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Groupleader: Walter Nickel
Walter Nickel
Unconventional Protein Secretion
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Research
Our lab investigates unconventional mechanisms of protein secretion from mammalian cells. Our primary model cargo protein is Fibroblast Growth Factor 2 (FGF2), a potent mitogen involved in tumor-induced angiogenesis (Fig.1):
Fig. 1: Cis elements in FGF2 required for unconventional secretion from tumor cells.
As illustrated below (Fig. 2), unconventional secretion of FGF2 occurs by direct translocation across plasma membranes, a process that involves sequential interactions of FGF2 with ATP1A1, Tec kinase and the phosphoinositide PI(4,5)P2 at the inner leaflet of the plasma membrane. The interaction with PI(4,5)P2 causes FGF2 to oligomerize and to insert into the plasma membrane forming a toroidal pore. Membrane inserted FGF2 oligomers are believed to serve as translocation intermediates that are disassembled by heparan sulfate proteoglycans at the outer leaflet of plasma membranes. This process results in directional translocation of FGF2 from the cytoplasm into extracellular space.
Fig. 2: The unconventional secretory pathway of FGF2
Current research goals in the lab relate to the spatio-temporal coordination of FGF2 secretion in living cells, the analysis of the molecular mechanism by which FGF2 physically traverses the plasma membrane and the relevance of this process for other unconventional secretory proteins such as HIV Tat. Finally, the molecular mechanism of FGF2 secretion is used in the lab to develop inhibitors of this process with great potential for the development of drugs for cancer therapy that block the function of FGF2 as a tumor cell survival factor.
For further reading please download the review articles (download pdf) below.
Palotta and Nickel 2020 JCS.pdf
Dimou and Nickel 2018 Curr. Biol.pdf
La Venuta et al 2015 JBC.pdf
Nickel and Steringer 2014 J Mol Biol.pdf
Nickel and Rabouille 2012 J Cell Sci.pdf
Nickel 2011 Traffic.pdf
Nickel and Rabouille 2009 Nat Rev Mol Cell Bio.pdf
Nickel and Seedorf 2008 Annu Rev Cell Dev Biol.pdf
CV
| 2021 - | Managing Director of the Heidelberg University Biochemistry Center (BZH) |
| 2019 - | Dean of Studies of the Bachelor and Master programs in Biochemistry at Heidelberg University; Board member of the Faculty of Biosciences at Heidelberg University |
| 2016 - | Speaker and Founding Chair of the DFG Collaborative Research Center SFB/TRR 186 Heidelberg/Berlin: Molecular Switches in the Spatio-Temporal Control of Cellular Signal Transmission |
| 2010 - 2015 | Speaker of the DFG Graduate School GRK1188 "Quantitative Analysis of Dynamic Processes in Membrane Transport and Translocation” at Heidelberg University |
| 2004 - | Professor of Biochemistry at Heidelberg University Biochemistry Center (BZH) Faculty of Biosciences |
| 2001 - 2004 | Principal Investigator at Heidelberg University Biochemistry Center (BZH) |
| 2001 | Venia legendi in Biochemistry (appointment as university lecturer), Medical Faculty, University of Heidelberg, Germany |
| 1997-2000 | Post-doctoral research fellow (supported by a Feodor Lynen fellowship from the Alexander von Humboldt foundation and a fellowship from the Human Frontiers Science Program) in the laboratory of Prof. Dr. James E. Rothman, Cellular Biochemistry and Biophysics Program, Memorial Sloan-Kettering Cancer Center, New York, U.S.A. |
| 1994-1997 | Post-doctoral research fellow (supported by a fellowship from the German Research Foundation) in the laboratory of Prof. Dr. Felix T. Wieland, Institute for Biochemistry I, University of Heidelberg, Germany |
| 1994 | Graduation (Dr. rer. nat.; Georg August Universität Göttingen) |
| 1991-1994 | University of Göttingen, Germany, Department for Clinical Biochemistry (Laboratory of Prof. Dr. Hans-Dieter Söling) |
| 1991 | Diploma in Biology (Georg August Universität Göttingen) |
| 1990-1991 | Max Planck Institute for Experimental Medicine, Department for Chemistry, Göttingen, Germany (Laboratory of Prof. Dr. Frank Grosse) |
| 1988-1989 | Max Planck Institute for Experimental Medicine, Department for Chemistry, Göttingen, Germany (Laboratory of Prof. Dr. Fritz Eckstein) |
| 1985-1990 | University of Göttingen, Program of Study: Biology Major: Biochemistry, Minor: Microbiology, Organic Chemistry |
Lab Members
From left to right: Carola Sparn (PhD Student), Carmelo Tempra (Guest Scientist), Federica Scollo (Guest Scientist), Fabio Lolicato (Postdoc), Sabine Wegehingel (Technical Assistant), Daniel Beyer (PhD Student), Julia Steringer (Postdoc), Annalena Meyer (PhD Student), Roberto Saleppico (PhD Student), Hans-Michael Müller (Senior Postdoc), Walter Nickel, Anke Heymann (Administrative Assistant), and Jaime Fernandez Sobaberas (PhD Student)
Anke Heymann
Adminstrative Assistant
Adminstrative Assistant
Lab:Room 309 / Phone: +49 6221 54-4160
Mail:anke.heymann@bzh.uni-heidelberg.de
Margot Ruland
Adminstrative Assistant (SFB/TRR 186)
Adminstrative Assistant (SFB/TRR 186)
Lab:Room 307 / Phone: +49 6221 54-4491
Mail:margot.ruland@bzh.uni-heidelberg.de
Daniel Beyer
PhD student
PhD student
Lab:Room 323
/ Phone: +49 6221 54-4746
Mail:daniel.beyer@bzh.uni-heidelberg.de
.JPG)
Jaime Fernandez Sobaberas
PhD student
PhD student
Lab:Room 322
/ Phone: +49 6221 54-5428
Mail:jaime.fernandez-sobaberas@bzh.uni-heidelberg.de
Manpreet Kaur
PhD student
PhD student
Lab:Room 322
/ Phone: +49 6221 54-5428
Mail:manpreet.kaur@bzh.uni-heidelberg.de
Ali Lashkari
PhD student
PhD student
Lab:Room 321
/ Phone: +49 6221 54-5427
Mail:ali.lashkari@bzh.uni-heidelberg.de
Fabio Lolicato
postdoc
postdoc
Lab:Room 321
/ Phone: +49 6221 54-5427
Office:Room 305
/ Phone: +49 6221 54-4351
Mail:fabio.lolicato@bzh.uni-heidelberg.de
Annalena Meyer
PhD student
PhD student
Lab:Room 321
/ Phone: +49 6221 54-5427
Mail:annalena.meyer@bzh.uni-heidelberg.de
Hans-Michael Müller
staff scientist
staff scientist
Lab:Room 322
/ Phone: +49 6221 54-5428
Office:Room 306
/ Phone: +49 6221 54-4180
Mail:hans-michael.mueller@bzh.uni-heidelberg.de
Roberto Saleppico
PhD student
PhD student
Lab:Room 321
/ Phone: +49 6221 54-5427
Mail:roberto.saleppico@bzh.uni-heidelberg.de
Julia Steringer
postdoc
postdoc
Lab:Room 321
/ Phone: +49 6221 54-5427
Mail:julia.steringer@bzh.uni-heidelberg.de
Sabine Wegehingel
TA
TA
Lab:Room 322
/ Phone: +49 6221 54-5428
Office:Room 306
/ Phone: +49 6221 54-4180
Mail:sabine.wegehingel@bzh.uni-heidelberg.de
Publications
Key publications
Sparn C, Dimou E, Meyer A, Saleppico R, Wegehingel S, Gerstner M, Klaus S, Ewers H, Nickel W (2022) Glypican-1 drives unconventional secretion of Fibroblast Growth Factor 2. eLife e75545
Legrand C, Saleppico R, Sticht J, Lolicato F, Müller HM, Wegehingel S, Dimou E, Steringer JP, Ewers E, Vattulainen I, Freund C, Nickel W (2020) The Na,K-ATPase acts upstream of phosphoinositide PI(4,5)P2 facilitating unconventional secretion of Fibroblast Growth Factor 2. Commun Biol 3:141
Dimou E, Cosentino K, Platonova E, Ros U, Sadeghi M, Kashyap P, Katsinelos T, Wegehingel S, Noé F, García-Sáez AJ, Ewers H, Nickel W (2019) Single event visualization of unconventional secretion of FGF2. J Cell Biol 218:683-699
Katsilenos T, Zeitler M, Dimou E, Karakatsani A, Müller HM, Nachman E, Steringer JP, Ruiz de Almodovar C, Nickel W#, Jahn TR#(2018) Unconventional secretion mediates the trans-cellular spreading of Tau. Cell Reports 23:2039-2055 (# corresponding authors)
Steringer JP, Lange S, Čujová S, Šachl R, Poojari C, Lolicato F, Beutel O, Müller HM, Unger S, Coskun Ü, Honigmann A, Vattulainen I, Hof M, Freund C, Nickel W (2017) Key steps in unconventional secretion of fibroblast growth factor 2 reconstituted with purified components. eLife e28985
Müller HM, Steringer JP, Wegehingel S, Bleicken S, Münster M, Dimou E, Unger S, Weidmann G, Andreas H, García-Sáez AJ, Wild K, Sinning I, Nickel W (2015) Formation of disulfide bridges drives oligomerization, membrane pore formation, and translocation of fibroblast growth factor 2 to cell surfaces. J Biol Chem 290:8925-8937
Steringer JP, Bleicken S, Andreas H, Zacherl S, Laussmann M, Temmerman K, Contreras FX, Bharat TA, Lechner J, Müller HM, Briggs JA, García-Sáez AJ, Nickel W (2012) Phosphatidylinositol 4,5-bisphosphate [PI(4,5)P2]-dependent oligomerization of fibroblast growth factor 2 (FGF2) triggers the formation of a lipidic membrane pore implicated in unconventional secretion.
J Biol Chem 287:27659-27669
Ebert AD, Laussmann M, Wegehingel S, Kaderali L, Erfle H, Reichert J, Lechner J, Beer HD, Pepperkok R, Nickel W (2010) Tec-kinase-mediated phosphorylation of fibroblast growth factor 2 is essential for unconventional secretion. Traffic 11:813-826
Zehe C, Engling A, Wegehingel S, Schäfer T, Nickel W (2006) Cell-surface heparan sulfate proteoglycans are essential components of the unconventional export machinery of FGF-2.
Proc. Natl. Acad. Sci. U.S.A. 103:15479-15484
Seelenmeyer C, Wegehingel S, Tews I, Künzler M, Aebi M, Nickel W (2005) Cell surface counter receptors are essential components of the unconventional export machinery of galectin-1.
J. Cell Biol. 17:373-381
Reviews on unconventional protein secretion
Sparn C, Meyer, A, Saleppico R, and Nickel W (2022) Unconventional secretion mediated by direct protein self-translocation across the plasma membranes of mammalian cells.
Trends Biochem Sci, in press
Lolicato F and Nickel W (2022) A role for liquid-ordered plasma membrane nanodomains coordinating the unconventional secretory pathway of Fibroblast Groth Factor 2.
Front Cell Dev Biol 10:864257
Pallotta MT and Nickel W (2020) FGF2 and IL-1β: Explorers of unconventional secrtory pathways.
J Cell Sci 133(21):jcs250449
Dimou E and Nickel W (2018) Unconventional mechanisms of eukaryotic protein secretion.
Curr Biol 28:R406-R410
Complete list of publications:
Walter Nickel at PubMed
A Role for Liquid-Ordered Plasma Membrane Nanodomains Coordinating the Unconventional Secretory Pathway of Fibroblast Growth Factor 2? Front Cell Dev Biol. 2022 Apr 1;10:864257.
doi: 10.3389/fcell.2022.864257. eCollection 2022. Lolicato, F., Nickel, W. (2022)
Glypican-1 drives unconventional secretion of Fibroblast Growth Factor 2. Elife. 2022 Mar 29;11:e75545. doi: 10.7554/eLife.75545. Online ahead of print. Sparn, C., Dimou, E., Meyer, A., Saleppico, R., Wegehingel, S., Gerstner, M., Klaus, S., Ewers, H. & Nickel, W. (2022)
Unconventional secretion mediated by direct protein self-translocation across the plasma membranes of mammalian cells, Trends Biochem Sci. 2022 Apr 27;S0968-0004(22)00086-X.
doi: 10.1016/j.tibs.2022.04.001. Online ahead of print. Sparn, C., Meyer, A., Saleppico, R., Nickel, W. (2022)
Unconventional secretion mediated by direct protein self-translocation across the plasma membranes of mammalian cells. Trends Biochem Sci. 2022 Apr 27;S0968-0004(22)00086-X.
doi: 10.1016/j.tibs.2022.04.001. Online ahead of print. Sparn, C., Meyer, A., Saleppico, R., Nickel, W. (2022)
Cholesterol promotes both head group visibility and clustering of PI(4,5)P2 driving unconventional secretion of Fibroblast Growth Factor 2. https://www.biorxiv.org/content/10.1101/2021.04.16.440132v1 Lolicato, F., Saleppico, R., Griffo, A., Pokrandt, B., Müller, H.M., Ewers, H, Hähl, H, Fleury, J.P., Seemann, R., Brügger, B., Jacobs, K., Vattulainen, I. & Nickel, W. (2021)
Identification of cis-acting determinants mediating the unconventional secretion of tau. Sci Rep 11, 12946. https://doi.org/10.1038/s41598-021-92433-3 Katsinelos, T., McEwan, W.A., Jahn, T.R. & Nickel, W. (2021)
FGF2 and IL-1β: Explorers of unconventional secrtory pathways. J Cell Sci 133(21):jcs250449.
Pallotta MT and Nickel W (2020)
Functional assay to correlate protein oligomerization states with membrane pore formation. Anal Chem 92(22):14861-14866.
Sachl R, Cujova S, Singh V, Riegerova P, Kapusta P, Müller HM, Steringer JP, Hof M and Nickel W (2020)
The Na,K-ATPase acts upstream of phosphoinositide PI(4,5)P2 facilitating unconventional secretion of Fibroblast Growth Factor 2. Commun Biol 3:141.
Legrand C, Saleppico R, Sticht J, Lolicato F, Müller HM, Wegehingel S, Dimou E, Steringer JP, Ewers E, Vattulainen I, Freund C, Nickel W (2020)
A time-resolved live cell imaging assay to identify small molecule inhibitors of FGF2 signaling. FEBS Lett. 593:2162-2176.
Ahmed M, Legrand C, Yagüe Relimpio A, Beretta CA, Muschko A, Wegehingel S, Müller HM, Sehr P, Will DW, Lewis JD, Nickel W (2019)
Single event visualization of unconventional secretion of FGF2. J Cell Biol 218:683-699.
Dimou E, Cosentino K, Platonova, E, Ros U, Sadeghi M, Kashyap P, Katsinelos T, Wegehingel S, Noé F, García-Saéz AJ, Ewers H, Nickel W (2019)
The molecular mechanism underlying unconventional secretion of Fibroblast Growth Factor 2 from tumour cells. Sem Cell Dev Biol, PMID:29458182.
Steringer JP and Nickel W (2018)
Unconventional mechanisms of eukaryotic protein secretion. Curr Biol 28:R406-R410.
Dimou E and Nickel W (2018)
Unconventional protein secretion: Diversity and consensus. Sem Cell Dev Biol, PMID:29549063.
Nickel W and Rabouille C (2018)
Unconventional Secretion Mediates the Trans-cellular Spreading of Tau. Cell reports, 23(7), 2039–2055. https://doi.org/10.1016/j.celrep.2018.04.056 Katsinelos, T., Zeitler, M., Dimou, E., Karakatsani, A., Müller, H.M., Nachman, E., Steringer, J.P., Ruiz de Almodovar, C., Nickel, W., & Jahn, T.R. (2018)
An emerging case for membrane pore formation as a common mechanism for the unconventional secretion of FGF2 and IL-1beta. J. Cell Sci 130:3197-3202.
Brough D, Pellegrin P, and Nickel W (2017)
Key steps in unconventional secretion of fibroblast growth factor 2 reconstituted with purified components. eLife (e28985).
Steringer JP, Lange S, Čujová S, Šachl R, Poojari C, Lolicato F, Beutel O, Müller HM, Unger S, Coskun Ü, Honigmann A, Vattulainen I, Hof M, Freund C, Nickel W (2017)
The molecular mechanism underlying unconventional secretion of fibroblast growth factor 2 from tumor cells. Biol. Cell 109:375-380.
Steringer JP and Nickel W (2017)
Tyrosine Kinase Expressed in Hepatocellular Carcinoma, TEC, Controls Pluripotency and Early Cell Fate Decisions of Human Pluripotent Stem Cells via Regulation of Fibroblast Growth Factor-2 Secretion. Stem Cells 35:2050-2059.
Vanova T, Konecna Z, Zbonakova Z, La Venuta G, Zoufalova K, Jelinkova S, Varecha M, Rotrekl V, Krejci P, Nickel W, Dvorak P, Kunova-Bosakova M (2017)
Inflammasome-dependent IL-1β release depends upon membrane permeabilisation. Cell Death Differ. 23:1219-31.
Martín-Sánchez F, Diamond C, Zeitler M, Gomez AI, Baroja-Mazo A, Bagnall J, Spiller D, White M, Daniels MJ, Mortellaro A, Peñalver M, Paszek P, Steringer JP, Nickel W, Brough D, Pelegrín P. (2016)
Small Molecule Inhibitors Targeting Tec Kinase Block Unconventional Secretion of Fibroblast Growth Factor 2. J. Biol. Chem. 291:17787-803.
La Venuta G, Wegehingel S, Sehr P, Müller HM, Dimou E, Steringer JP, Grotwinkel M, Hentze N, Mayer MP, Will DW, Uhrig U, Lewis JD, Nickel W (2016)
Sphingosine-1-Phosphate Lyase Deficient Cells as a Tool to Study Protein Lipid Interactions. PLOS ONE 11(4): e0153009. https://doi.org/10.1371/journal.pone.0153009 Gerl, M.J., Bittl, V., Kirchner, S., Sachsenheimer, T., Brunner, H.L., Lüchtenborg, C., Özbalci, C., Wiedemann, H., Wegehingel, S., Nickel, W., Haberkant, P., Schultz, C., Krüger, M., & Brügger, B. (2016)
A Dual SILAC Proteomic Labeling Strategy for Quantifying Constitutive and Cell-Cell Induced Protein Secretion. J. Proteome Res. 14, 8, 3229–3238. https://doi.org/10.1021/acs.jproteome.5b00199 Stiess M, Wegehingel S, Nguyen C, Nickel W, Bradke F, Cambridge SB (2015)
Formation of Disulfide Bridges Drives oligomerization, membrane pore formation and translocation of fibroblast growth factor 2 to cell surfaces, J. Biol. Chem. 290: 8925-37. Müller, H.M., Steringer, J.S., Wegehingel, S., Bleicken, S., Münster, M., Dimou, E., Unger, S., Weidmann, G., Andreas H., Garcia-Saez, A., Wild, K., Sinning, I. & Nickel, W. (2015)
HIV-Tat Forms Phosphoinositide Dependent Membrane Pores Implicated in Unconventional Protein Secretion. J Biol Chem [Epub ahead of print].
Zeitler M, Steringer JP, Müller HM, Mayer MP, Nickel W (2015)
The Startling Properties of Fibroblast Growth Factor 2: How to Exit Mammalian Cells Without a Signal Peptide at Hand? J Biol Chem. pii: jbc.R115.689257. [Epub ahead of print].
La Venuta G, Zeitler M, Steringer JP, Müller HM, Nickel W (2015)
A direct role for ATP1A1 in unconventional secretion of fibroblast growth factor 2. J. Biol. Chem. 290:3654-3665.
Zacherl S, La Venuta G, Müller HM, Wegehingel S, Dimou E, Sehr P, Lewis JD, Erfle H, Pepperkok R, Nickel W (2014)
Dynamin-related protein 1 (Drp1) promotes structural intermediates of membrane division. J. Biol. Chem. 289:30645-30656.
Ugarte-Uribe B, Müller HM, Otsuki M, Nickel W, García-Sáez AJ. (2014)
Heterologous Src homology 4 domains support membrane anchoring and biological activity of HIV-1 Nef. J. Biol. Chem. 289:14030-14044.
Geist MM, Pan X, Bender S, Bartenschlager R, Nickel W, Fackler OT. (2014)
Unconventional secretion of fibroblast growth factor 2 -- A novel type of protein translocation across membranes? J. Mol. Biol. 427:1202-1210. Steringer JP, Müller HM, Nickel W (2014)
CDC42 switches IRSp53 from inhibition of actin growth to elongation by clustering of VASP. EMBO J. 32:2735-50.
Disanza A, Bisi S, Winterhoff M, Milanesi F, Ushakov DS, Kast D, Marighetti P, Romet- Lemonne G, Müller HM, Nickel W, Linkner J, Waterschoot D, Ampè C, Cortellino S, Palamidessi A, Dominguez R, Carlier MF, Faix J, Scita G. (2013)
Chromosome segregation by the Escherichia coli Min system. Mol Syst Biol. 2013;9:686.
Di Ventura B, Knecht B, Andreas H, Godinez WJ, Fritsche M, Rohr K, Nickel W, Heermann DW, Sourjik V. (2013)
Differential transport of Influenza A neuraminidase signal anchor peptides to the plasma membrane. FEBS letters, 587(9), 1411–1417. https://doi.org/10.1016/j.febslet.2013.03.019 Ernst, A. M., Zacherl, S., Herrmann, A., Hacke, M., Nickel, W., Wieland, F. T., & Brügger, B. (2013)
HIV-1 Nef disrupts membrane- microdomain-associated anterograde transport for plasma membrane delivery of selected Src family kinases. Cell Microbiol. 15:1605-21.
Pan X, Geist MM, Rudolph JM, Nickel W, Fackler OT (2013)
Oligomerization and Ca2+/calmodulin control binding of the ER Ca2+-sensors STIM1 and STIM2 to plasma membrane lipids. Biosci Rep. 2013 Oct 31;33(5). (pii: e00077. doi: 10.1042/BSR20130089).
Bhardwaj R, Müller HM, Nickel W, Seedorf M. (2013)
Diversity in unconventional protein secretion. J Cell Sci. 125:5251-5.
Rabouille C, Malhotra V, Nickel W. (2012)
Loss of ceramide synthase 3 causes lethal skin barrier disruption. Hum Mol Genet. 21:586-608.
Jennemann R, Rabionet M, Gorgas K, Epstein S, Dalpke A, Rothermel U, Bayerle A, van der Hoeven F, Imgrund S, Kirsch J, Nickel W, Willecke K, Riezman H, Gröne HJ, Sandhoff R. (2012)
PI(4,5)P2-dependent oligomerization of fibroblast growth factor 2 (FGF2) triggers the formation of a lipidic membrane pore implicated in unconventional secretion. The Journal of biological chemistry, 287(33), 27659–27669. https://doi.org/10.1074/jbc.M112.381939 Steringer, J. P., Bleicken, S., Andreas, H., Zacherl, S., Laussmann, M., Temmerman, K., Contreras, F. X., Bharat, T. A., Lechner, J., Müller, H. M., Briggs, J. A., García-Sáez, A. J., & Nickel, W. (2012)
Trafficking and release of Leishmania metacyclic HASPB on macrophage invasion. Cell Microbiol. 14:740-761.
Maclean, LM, O'Toole, PJ, Stark, M, Marrison, J, Seelenmeyer, C, Nickel, W, and Smith, DF (2012)
Phenotypic profiling of the human genome reveals gene products involved in plasma membrane targeting of SRC kinases. Genome Res. 21(11):1955-68. Ritzerfeld J, Remmele S, Wang T, Temmerman K, Brügger B, Wegehingel S, Tournaviti S, Strating JR, Wieland FT, Neumann B, Ellenberg J, Lawerenz C, Hesser J, Erfle H, Pepperkok R, Nickel W. (2011)
Targeting of Nbp1 to the inner nuclear membrane is essential for spindle pole body duplication. EMBO J. 30(16):3337-52. Kupke T, Di Cecco L, Müller HM, Neuner A, Adolf F, Wieland F, Nickel W, Schiebel E. (2011)
The Unconventional Secretory Machinery of Fibroblast Growth Factor 2. Traffic 12:799-805.
Walter Nickel (2011)
Pathways of Unconventional Protein Secretion. Curr. Opin. Biotechnol. 21:621-626.
Walter Nickel (2010)
Tec-kinase-mediated phosphorylation of fibroblast growth factor 2 is essential for unconventional secretion. Traffic 11(6):813-26. Ebert AD, Laußmann M, Wegehingel S, Kaderali L, Erfle H, Reichert J, Lechner J, Beer HD, Pepperkok R, Nickel W. (2010)
A conserved, lipid-mediated mechanism for the sorting of yeast Ist2 and mammalian STIM proteins to plasma membrane-associated domains of the peripheral ER. Traffic 10:1802-1818.
Ebru Ercan, Frank Momburg, Ulrike Engel, Koen Temmerman, Walter Nickel and Matthias Seedorf (2009)
A lipid-binding motif targets the yeast integral membrane protein Ist2 to domains of the cortical ER. Traffic 10:1084-1097.
Marcel A. Fischer, Koen Temmerman, Walter Nickel and Matthias Seedorf (2009)
A novel flow cytometric assay to quantify interactions between proteins and membrane lipids. J. Lipid Res. 50:1245-1254.
Koen Temmerman and Walter Nickel (2009)
A signal comprising a basic cluster and an amphipathic α-helix interacts with lipids and is required for the transport of Ist2 to the yeast cortical ER. J. Cell Sci. 122:625-635.
Kiran Maass, Marcel André Fischer, Markus Seiler, Koen Temmerman, Walter Nickel and Matthias Seedorf (2009)
An Intrinsic Quality Control Mechanism Ensures Unconventional Secretion of Fibroblast Growth Factor 2 in a Folded Conformation. J. Cell Sci. 122:3322-3329.
Lucía Cespón Torrado, Koen Temmerman, Hans-Michael Müller, Matthias P. Mayer, Claudia Seelenmeyer, Rafael Backhaus, and Walter Nickel (2009)
Mechanisms of Regulated Unconventional Protein Secretion. Nat. Rev. Mol. Cell Biol. 10:148-155.
Walter Nickel and Catherine Rabouille (2009)
Reversible Phosphorylation as a Molecular Switch to Regulate Plasma Membrane Targeting of Acylated SH4 Domain Proteins. Traffic 10:1047-1060.
Stella Tournaviti, Enrica San Pietro, Stefan Terjung, Tobias Schafmeier, Sabine Wegehingel, Julia Ritzerfeld, Juliane Schulz, Deborah F. Smith, Rainer Pepperkok, and Walter Nickel (2009)
The Golgi-associated Protein p115 Mediates the Secretion of Macrophage Migration Inhibitory Factor. J. Immunol. 182:6896-6906.
Melanie Merk, John Baugh, Swen Zierow, Lin Leng, Utpal Pal, Seung Joon Lee, Antje D. Ebert, Yuka Mizue, John O. Trent, Robert Mitchell, Walter Nickel, Paula B. Kavathas, Jürgen Bernhagen, and Richard Bucala (2009)
Rerouting of Fibroblast Growth Factor 2 to the Classical Secretory Pathway Results in Post-translational Modifications That Block Binding to Heparan Sulfate Proteoglycans. FEBS Lett. 582:2387-2392.
Sabine Wegehingel, Christoph Zehe, and Walter Nickel (2008)
Unconventional Mechanisms of Protein Transport to the Cell Surface of Eukaryotic Cells. Annu. Rev. Cell Dev. Biol. 24:287-308.
Walter Nickel and Matthias Seedorf (2008)
Unconventional Secretion of Fibroblast Growth Factor 2 and Galectin-1 Does Not Require Shedding of Plasma-Membrane-Derived Vesicles. FEBS Lett. 582:1362-1368.
Claudia Seelenmeyer, Carolin Stegmayer, and Walter Nickel (2008)
SH4-domain-induced plasma membrane dynamization promotes bleb-associated cell motility. Journal of cell science, 120(Pt 21), 3820–3829. https://doi.org/10.1242/jcs.011130 Tournaviti, S., Hannemann, S., Terjung, S., Kitzing, T. M., Stegmayer, C., Ritzerfeld, J., Walther, P., Grosse, R., Nickel, W., & Fackler, O. T. (2007)
Unconventional Protein Secretion: An Extracellular Trap For Nonclassical Export of Fibroblast Growth Factor 2. J. Cell Sci. 120:2295-2299.
Walter Nickel (2007)
Cell surface heparan sulfate proteoglycans are essential components of the unconventional export machinery of FGF-2. Proc. Natl. Acad Sci. U.S.A. 103:15479-15484.
Christoph Zehe, André Engling, Sabine Wegehingel, Tobias Schäfer, and Walter Nickel (2006)
Cell Surface Counter Receptors are Essential Components of the Unconventional Export Machinery of Galectin-1. J. Cell Biol. 172:373-381.
Claudia Seelenmeyer, Sabine Wegehingel, Ivo Tews, Markus Künzler, Markus Aebi, and Walter Nickel (2005)
Direct Transport Across the Plasma Membrane of Mammalian Cells of Leishmania HASPB as Revealed by a CHO Export Mutant. J. Cell Sci. 118:517-527.
Carolin Stegmayer, Angelika Kehlenbach, Stella Tournaviti, Sabine Wegehingel, Christoph Zehe, Paul W. Denny, Deborah F. Smith, Blanche Schwappach, and Walter Nickel (2005)
Unconventional Secretory Routes: Direct Protein Export Across the Plasma Membrane of Mammalian Cells. Traffic 6:607-614.
Walter Nickel (2005)
Unconventional Protein Secretion: Membrane Translocation of FGF-2 Does Not Require Protein Unfolding. J. Cell Sci. 117:1727-1736.
Rafael Backhaus, Christoph Zehe, Sabine Wegehingel, Angelika Kehlenbach, Blanche Schwappach, and Walter Nickel (2004)
Unconventional secretion of fibroblast growth factor 2 is mediated by direct translocation across the plasma membrane of mammalian cells. J Biol Chem. 279(8):6244-51. Schäfer T, Zentgraf H, Zehe C, Brügger B, Bernhagen J, Nickel W. (2004)
Functional reconstitution of COPI coat assembly and disassembly using chemically defined components. Proc. Natl. Acad Sci. U.S.A. 100:8253-8257. Constanze Reinhard, Michael Schweikert, Felix T. Wieland, and Walter Nickel (2003)
Regulated secretion of macrophage migration inhibitory factor is mediated by a nonclassical pathway involving an ABC transporter. FEBS Lett. 551:78-86.
Oliver Flieger, André Engling, Richard Bucala, Hongqi Lue, Walter Nickel, and Jürgen Bernhagen (2003)
The Mystery of Non-classical Protein Secretion: A Current View on Cargo Proteins and Potential Export Routes. Eur. J. Biochem. 270:2109-2119.
Walter Nickel (2003)
Biosynthetic FGF-2 is Targeted to Non-Lipid Raft Microdomains Following Translocation to the Extracellular Surface of CHO cells. J. Cell Sci. 115:3619-3631.
André Engling, Rafael Backhaus, Carolin Stegmayer, Christoph Zehe, Claudia Seelenmeyer, Angelika Kehlenbach, Blanche Schwappach, Sabine Wegehingel, and Walter Nickel (2002)
Vesicular transport: the core machinery of COPI recruitment and budding. J Cell Sci. 115(Pt 16):3235-40. Review. Nickel W, Brügger B, Wieland FT. (2002)
Membrane Trafficking: How Transport Vesicles Fuse With Target Membranes in "Protein Modules in Cellular Signalling", eds Heilmeyer L. and Friedrich P. (IOS Press Amsterdam), pp. 257-261 (Review). Walter Nickel, Britta Brügger and Felix T. Wieland (2001)
Molecular Mechanisms of COPI Vesicle Formation in "Protein Modules in Cellular Signalling", eds. Heilmeyer L. and Friedrich P. (IOS Press Amsterdam), pp. 262-267 (Review). Britta Brügger, Walter Nickel, and Felix T. Wieland (2001)
Recruitment to Golgi membranes of ADP-ribosylation factor 1 is mediated by the cytoplasmic domain of p23. The EMBO journal, 20(23), 6751–6760. https://doi.org/10.1093/emboj/20.23.6751 Gommel, D. U., Memon, A. R., Heiss, A., Lottspeich, F., Pfannstiel, J., Lechner, J., Reinhard, C., Helms, J. B., Nickel, W., & Wieland, F. T. (2001)
Allosteric activation of acid a-glucosidase by the human papillomavirus E7 protein. J. Biol. Chem. 275:9534-9541.
Werner Zwerschke, Boris Mannhardt, Paola Massimi, Sonja Nauenburg, David Pim, Walter Nickel, Lawrence Banks, Arnold J. Reuser, Pidder Jansen-Dürr (2000)
Evidence for segregation of sphingomyelin and cholesterol during formation of COPI-coated vesicles. J Cell Biol. 151(3):507-18. Brügger B, Sandhoff R, Wegehingel S, Gorgas K, Malsam J, Helms JB, Lehmann WD, Nickel W, Wieland FT. (2000)
Functional Architecture of Intracellular t-SNAREs: Membrane Fusion by Isolated SNAREs of the Yeast Vacuole. Nature 407:198-202. Ryouichi Fukuda, James A. McNew, Thomas Weber, Francesco Parlati, Thomas Engel, Walter Nickel, James E. Rothman, and Thomas H. Söllner (2000)
Putative fusogenic activity of NSF is restricted to a lipid mixture whose coalescence is also triggered by other factors. EMBO J. 19(6):1272-8. Brügger B, Nickel W, Weber T, Parlati F, McNew JA, Rothman JE, Söllner T. (2000)
Receptor-Dependent Formation of COPI-Coated Vesicles From Chemically Defined Donor Liposomes. Methods Enzymol. 329:388-404. Walter Nickel and Felix T. Wieland (2000)
A role for ADP-ribosylation factor in the control of cargo uptake during COPI-coated vesicle biogenesis. FEBS Lett. 462:267-272. Jörg Malsam, Daniel Gommel, Felix. T. Wieland, and Walter Nickel (1999)
Content mixing and membrane integrity during membrane fusion driven by pairing of isolated v-SNAREs and t-SNAREs. Proc. Natl. Acad Sci. U.S.A. 96 :12571-12576. Walter Nickel, Thomas Weber, James A. McNew, Francesco Parlati, Thomas H. Söllner, and James E. Rothman (1999)
COPI-Mediated Protein and Lipid Sorting. Protoplasma 207:115-124 (Review). Walter Nickel and Britta Brügger (1999)
Coupling of coat assembly and vesicle budding to packaging of putative cargo receptors. Cell 96, 495-506. M. Bremser, W. Nickel, M. Schweikert, M. Ravazzola, M. Amherd, C.A. Hughes, T.H. Söllner, J. E. Rothman, and F. T. Wieland (1999)
p24 and p23, the major transmem-brane proteins of COPI-coated transport vesicles, form hetero-oligomeric complexes and cycle between the organelles of the early secretory pathway. FEBS Lett. 447:179-185. D. Gommel, L. Orci, E.M. Emig, M.J. Hannah, M. Ravazzola, W. Nickel, J.B. Helms, F.T. Wieland and K. Sohn (1999)
A putative heterotrimeric G protein inhibits the fusion of COPI-coated vesicles. Segregation of heterotrimeric G proteins from COPI-coated vesicles. J Biol Chem. 273(24):15203-8. Helms JB, Helms-Brons D, Brügger B, Gkantiragas I, Eberle H, Nickel W, Nürnberg B, Gerdes HH, Wieland FT. (1998)
Biosynthetic Protein Transport Through the Early Secretory Pathway. Histochem. Cell Biol. 109:477-486 (Review). Walter Nickel and Felix T. Wieland (1998)
Intracellular Transport of Glycoproteins and Glycolipids. Trends Glycosci. Glycotechnolog. 10:1-11 (Review). Walter Nickel, Britta Brügger, and Felix T. Wieland (1998)
Protein and lipid sorting between the endoplasmic reticulum and the Golgi complex. Semin Cell Dev Biol. 9(5):493-501. Review. Nickel W, Brügger B, Wieland FT. (1998)
Uptake by COPI-coated vesicles of both anterograde and retrograde cargo is inhibited by GTPgammaS in vitro. J. Cell Sci. 111:3081-3090. Walter Nickel, Jörg Malsam, Karin Gorgas, Mariella Ravazzola, Nicole Jenne, J. Bernd Helms, and Felix T. Wieland (1998)
Biogenesis of COPI-Coated Transport Vesicles. FEBS Lett. 413:395-400 (Review). Walter Nickel and Felix T. Wieland (1997)
p23, a major COPI-vesicle membrane protein, constitutively cycles through the early secretory pathway. Proc. Natl. Acad. Sci. U.S.A. 94, 11393-11398. W. Nickel, K. Sohn, C. Bünning, and F. Wieland (1997)
Protein-Reifung: Transport, Faltung und Abbau. Biospektrum 4: 22-24 (Review).
Walter Nickel and Klaus Leitzgen (1997)
Forskolin stimulates detoxification of brefeldin A. J. Biol. Chem. 271:15870-15873. Walter Nickel, J. Bernd Helms, Richard E. Kneusel, and Felix T. Wieland (1996)
Sorting and budding of constitutive secretory vesicles in hepatocytes and hepatoma cells. Adv. Enzyme Regul. 35:283-292.
Andreas Barthel, Walter Nickel, Christiane Tonko, and Hans-Dieter Söling (1995)
ADP-ribosylation factor (ARF) and a 14 kDa Polypeptide Are Associated With Heparan Sulfate Proteoglycan-carrying Post-trans-Golgi network Secretory Vesicles. J. Cell Biol. 125:721-731.
Walter Nickel, Lukas A. Huber, Richard A. Kahn, Nicola Kipper, Andreas Barthel, Dirk Faßhauer, and Hans-Dieter Söling (1994)
ARF and VAPP14: Two Proteins Involved in the Delivery of Heparan Sulfate Proteoglycan From the TGN to the Cell Surface. Ann. NY Acad. Sci. 1994:344-356.
Walter Nickel, Richard A. Kahn, Nicola Kipper, Andreas Barthel, Dirk Faßhauer, and Hans-Dieter Söling (1994)
Funktionelle und strukturelle Untersuchungen zum vesikulären Golgi-Plasmamembran-Transport in Leberzellen. PhD thesis. Georg-August-Universität Göttingen. ©Cuvillier-Verlag Göttingen.
Walter Nickel (1994)
Interactions of Azidothymidine Triphosphate with the Cellular DNA Polymerases alpha, delta and epsilon and with DNA Primase. J. Biol. Chem. 267:848-854.
Walter Nickel, Sabine Austermann, Gabriele Bialek, and Frank Grosse (1992)
doi: 10.3389/fcell.2022.864257. eCollection 2022. Lolicato, F., Nickel, W. (2022)
Glypican-1 drives unconventional secretion of Fibroblast Growth Factor 2. Elife. 2022 Mar 29;11:e75545. doi: 10.7554/eLife.75545. Online ahead of print. Sparn, C., Dimou, E., Meyer, A., Saleppico, R., Wegehingel, S., Gerstner, M., Klaus, S., Ewers, H. & Nickel, W. (2022)
Unconventional secretion mediated by direct protein self-translocation across the plasma membranes of mammalian cells, Trends Biochem Sci. 2022 Apr 27;S0968-0004(22)00086-X.
doi: 10.1016/j.tibs.2022.04.001. Online ahead of print. Sparn, C., Meyer, A., Saleppico, R., Nickel, W. (2022)
Unconventional secretion mediated by direct protein self-translocation across the plasma membranes of mammalian cells. Trends Biochem Sci. 2022 Apr 27;S0968-0004(22)00086-X.
doi: 10.1016/j.tibs.2022.04.001. Online ahead of print. Sparn, C., Meyer, A., Saleppico, R., Nickel, W. (2022)
Cholesterol promotes both head group visibility and clustering of PI(4,5)P2 driving unconventional secretion of Fibroblast Growth Factor 2. https://www.biorxiv.org/content/10.1101/2021.04.16.440132v1 Lolicato, F., Saleppico, R., Griffo, A., Pokrandt, B., Müller, H.M., Ewers, H, Hähl, H, Fleury, J.P., Seemann, R., Brügger, B., Jacobs, K., Vattulainen, I. & Nickel, W. (2021)
Identification of cis-acting determinants mediating the unconventional secretion of tau. Sci Rep 11, 12946. https://doi.org/10.1038/s41598-021-92433-3 Katsinelos, T., McEwan, W.A., Jahn, T.R. & Nickel, W. (2021)
FGF2 and IL-1β: Explorers of unconventional secrtory pathways. J Cell Sci 133(21):jcs250449.
Pallotta MT and Nickel W (2020)
Functional assay to correlate protein oligomerization states with membrane pore formation. Anal Chem 92(22):14861-14866.
Sachl R, Cujova S, Singh V, Riegerova P, Kapusta P, Müller HM, Steringer JP, Hof M and Nickel W (2020)
The Na,K-ATPase acts upstream of phosphoinositide PI(4,5)P2 facilitating unconventional secretion of Fibroblast Growth Factor 2. Commun Biol 3:141.
Legrand C, Saleppico R, Sticht J, Lolicato F, Müller HM, Wegehingel S, Dimou E, Steringer JP, Ewers E, Vattulainen I, Freund C, Nickel W (2020)
A time-resolved live cell imaging assay to identify small molecule inhibitors of FGF2 signaling. FEBS Lett. 593:2162-2176.
Ahmed M, Legrand C, Yagüe Relimpio A, Beretta CA, Muschko A, Wegehingel S, Müller HM, Sehr P, Will DW, Lewis JD, Nickel W (2019)
Single event visualization of unconventional secretion of FGF2. J Cell Biol 218:683-699.
Dimou E, Cosentino K, Platonova, E, Ros U, Sadeghi M, Kashyap P, Katsinelos T, Wegehingel S, Noé F, García-Saéz AJ, Ewers H, Nickel W (2019)
The molecular mechanism underlying unconventional secretion of Fibroblast Growth Factor 2 from tumour cells. Sem Cell Dev Biol, PMID:29458182.
Steringer JP and Nickel W (2018)
Unconventional mechanisms of eukaryotic protein secretion. Curr Biol 28:R406-R410.
Dimou E and Nickel W (2018)
Unconventional protein secretion: Diversity and consensus. Sem Cell Dev Biol, PMID:29549063.
Nickel W and Rabouille C (2018)
Unconventional Secretion Mediates the Trans-cellular Spreading of Tau. Cell reports, 23(7), 2039–2055. https://doi.org/10.1016/j.celrep.2018.04.056 Katsinelos, T., Zeitler, M., Dimou, E., Karakatsani, A., Müller, H.M., Nachman, E., Steringer, J.P., Ruiz de Almodovar, C., Nickel, W., & Jahn, T.R. (2018)
An emerging case for membrane pore formation as a common mechanism for the unconventional secretion of FGF2 and IL-1beta. J. Cell Sci 130:3197-3202.
Brough D, Pellegrin P, and Nickel W (2017)
Key steps in unconventional secretion of fibroblast growth factor 2 reconstituted with purified components. eLife (e28985).
Steringer JP, Lange S, Čujová S, Šachl R, Poojari C, Lolicato F, Beutel O, Müller HM, Unger S, Coskun Ü, Honigmann A, Vattulainen I, Hof M, Freund C, Nickel W (2017)
The molecular mechanism underlying unconventional secretion of fibroblast growth factor 2 from tumor cells. Biol. Cell 109:375-380.
Steringer JP and Nickel W (2017)
Tyrosine Kinase Expressed in Hepatocellular Carcinoma, TEC, Controls Pluripotency and Early Cell Fate Decisions of Human Pluripotent Stem Cells via Regulation of Fibroblast Growth Factor-2 Secretion. Stem Cells 35:2050-2059.
Vanova T, Konecna Z, Zbonakova Z, La Venuta G, Zoufalova K, Jelinkova S, Varecha M, Rotrekl V, Krejci P, Nickel W, Dvorak P, Kunova-Bosakova M (2017)
Inflammasome-dependent IL-1β release depends upon membrane permeabilisation. Cell Death Differ. 23:1219-31.
Martín-Sánchez F, Diamond C, Zeitler M, Gomez AI, Baroja-Mazo A, Bagnall J, Spiller D, White M, Daniels MJ, Mortellaro A, Peñalver M, Paszek P, Steringer JP, Nickel W, Brough D, Pelegrín P. (2016)
Small Molecule Inhibitors Targeting Tec Kinase Block Unconventional Secretion of Fibroblast Growth Factor 2. J. Biol. Chem. 291:17787-803.
La Venuta G, Wegehingel S, Sehr P, Müller HM, Dimou E, Steringer JP, Grotwinkel M, Hentze N, Mayer MP, Will DW, Uhrig U, Lewis JD, Nickel W (2016)
Sphingosine-1-Phosphate Lyase Deficient Cells as a Tool to Study Protein Lipid Interactions. PLOS ONE 11(4): e0153009. https://doi.org/10.1371/journal.pone.0153009 Gerl, M.J., Bittl, V., Kirchner, S., Sachsenheimer, T., Brunner, H.L., Lüchtenborg, C., Özbalci, C., Wiedemann, H., Wegehingel, S., Nickel, W., Haberkant, P., Schultz, C., Krüger, M., & Brügger, B. (2016)
A Dual SILAC Proteomic Labeling Strategy for Quantifying Constitutive and Cell-Cell Induced Protein Secretion. J. Proteome Res. 14, 8, 3229–3238. https://doi.org/10.1021/acs.jproteome.5b00199 Stiess M, Wegehingel S, Nguyen C, Nickel W, Bradke F, Cambridge SB (2015)
Formation of Disulfide Bridges Drives oligomerization, membrane pore formation and translocation of fibroblast growth factor 2 to cell surfaces, J. Biol. Chem. 290: 8925-37. Müller, H.M., Steringer, J.S., Wegehingel, S., Bleicken, S., Münster, M., Dimou, E., Unger, S., Weidmann, G., Andreas H., Garcia-Saez, A., Wild, K., Sinning, I. & Nickel, W. (2015)
HIV-Tat Forms Phosphoinositide Dependent Membrane Pores Implicated in Unconventional Protein Secretion. J Biol Chem [Epub ahead of print].
Zeitler M, Steringer JP, Müller HM, Mayer MP, Nickel W (2015)
The Startling Properties of Fibroblast Growth Factor 2: How to Exit Mammalian Cells Without a Signal Peptide at Hand? J Biol Chem. pii: jbc.R115.689257. [Epub ahead of print].
La Venuta G, Zeitler M, Steringer JP, Müller HM, Nickel W (2015)
A direct role for ATP1A1 in unconventional secretion of fibroblast growth factor 2. J. Biol. Chem. 290:3654-3665.
Zacherl S, La Venuta G, Müller HM, Wegehingel S, Dimou E, Sehr P, Lewis JD, Erfle H, Pepperkok R, Nickel W (2014)
Dynamin-related protein 1 (Drp1) promotes structural intermediates of membrane division. J. Biol. Chem. 289:30645-30656.
Ugarte-Uribe B, Müller HM, Otsuki M, Nickel W, García-Sáez AJ. (2014)
Heterologous Src homology 4 domains support membrane anchoring and biological activity of HIV-1 Nef. J. Biol. Chem. 289:14030-14044.
Geist MM, Pan X, Bender S, Bartenschlager R, Nickel W, Fackler OT. (2014)
Unconventional secretion of fibroblast growth factor 2 -- A novel type of protein translocation across membranes? J. Mol. Biol. 427:1202-1210. Steringer JP, Müller HM, Nickel W (2014)
CDC42 switches IRSp53 from inhibition of actin growth to elongation by clustering of VASP. EMBO J. 32:2735-50.
Disanza A, Bisi S, Winterhoff M, Milanesi F, Ushakov DS, Kast D, Marighetti P, Romet- Lemonne G, Müller HM, Nickel W, Linkner J, Waterschoot D, Ampè C, Cortellino S, Palamidessi A, Dominguez R, Carlier MF, Faix J, Scita G. (2013)
Chromosome segregation by the Escherichia coli Min system. Mol Syst Biol. 2013;9:686.
Di Ventura B, Knecht B, Andreas H, Godinez WJ, Fritsche M, Rohr K, Nickel W, Heermann DW, Sourjik V. (2013)
Differential transport of Influenza A neuraminidase signal anchor peptides to the plasma membrane. FEBS letters, 587(9), 1411–1417. https://doi.org/10.1016/j.febslet.2013.03.019 Ernst, A. M., Zacherl, S., Herrmann, A., Hacke, M., Nickel, W., Wieland, F. T., & Brügger, B. (2013)
HIV-1 Nef disrupts membrane- microdomain-associated anterograde transport for plasma membrane delivery of selected Src family kinases. Cell Microbiol. 15:1605-21.
Pan X, Geist MM, Rudolph JM, Nickel W, Fackler OT (2013)
Oligomerization and Ca2+/calmodulin control binding of the ER Ca2+-sensors STIM1 and STIM2 to plasma membrane lipids. Biosci Rep. 2013 Oct 31;33(5). (pii: e00077. doi: 10.1042/BSR20130089).
Bhardwaj R, Müller HM, Nickel W, Seedorf M. (2013)
Diversity in unconventional protein secretion. J Cell Sci. 125:5251-5.
Rabouille C, Malhotra V, Nickel W. (2012)
Loss of ceramide synthase 3 causes lethal skin barrier disruption. Hum Mol Genet. 21:586-608.
Jennemann R, Rabionet M, Gorgas K, Epstein S, Dalpke A, Rothermel U, Bayerle A, van der Hoeven F, Imgrund S, Kirsch J, Nickel W, Willecke K, Riezman H, Gröne HJ, Sandhoff R. (2012)
PI(4,5)P2-dependent oligomerization of fibroblast growth factor 2 (FGF2) triggers the formation of a lipidic membrane pore implicated in unconventional secretion. The Journal of biological chemistry, 287(33), 27659–27669. https://doi.org/10.1074/jbc.M112.381939 Steringer, J. P., Bleicken, S., Andreas, H., Zacherl, S., Laussmann, M., Temmerman, K., Contreras, F. X., Bharat, T. A., Lechner, J., Müller, H. M., Briggs, J. A., García-Sáez, A. J., & Nickel, W. (2012)
Trafficking and release of Leishmania metacyclic HASPB on macrophage invasion. Cell Microbiol. 14:740-761.
Maclean, LM, O'Toole, PJ, Stark, M, Marrison, J, Seelenmeyer, C, Nickel, W, and Smith, DF (2012)
Phenotypic profiling of the human genome reveals gene products involved in plasma membrane targeting of SRC kinases. Genome Res. 21(11):1955-68. Ritzerfeld J, Remmele S, Wang T, Temmerman K, Brügger B, Wegehingel S, Tournaviti S, Strating JR, Wieland FT, Neumann B, Ellenberg J, Lawerenz C, Hesser J, Erfle H, Pepperkok R, Nickel W. (2011)
Targeting of Nbp1 to the inner nuclear membrane is essential for spindle pole body duplication. EMBO J. 30(16):3337-52. Kupke T, Di Cecco L, Müller HM, Neuner A, Adolf F, Wieland F, Nickel W, Schiebel E. (2011)
The Unconventional Secretory Machinery of Fibroblast Growth Factor 2. Traffic 12:799-805.
Walter Nickel (2011)
Pathways of Unconventional Protein Secretion. Curr. Opin. Biotechnol. 21:621-626.
Walter Nickel (2010)
Tec-kinase-mediated phosphorylation of fibroblast growth factor 2 is essential for unconventional secretion. Traffic 11(6):813-26. Ebert AD, Laußmann M, Wegehingel S, Kaderali L, Erfle H, Reichert J, Lechner J, Beer HD, Pepperkok R, Nickel W. (2010)
A conserved, lipid-mediated mechanism for the sorting of yeast Ist2 and mammalian STIM proteins to plasma membrane-associated domains of the peripheral ER. Traffic 10:1802-1818.
Ebru Ercan, Frank Momburg, Ulrike Engel, Koen Temmerman, Walter Nickel and Matthias Seedorf (2009)
A lipid-binding motif targets the yeast integral membrane protein Ist2 to domains of the cortical ER. Traffic 10:1084-1097.
Marcel A. Fischer, Koen Temmerman, Walter Nickel and Matthias Seedorf (2009)
A novel flow cytometric assay to quantify interactions between proteins and membrane lipids. J. Lipid Res. 50:1245-1254.
Koen Temmerman and Walter Nickel (2009)
A signal comprising a basic cluster and an amphipathic α-helix interacts with lipids and is required for the transport of Ist2 to the yeast cortical ER. J. Cell Sci. 122:625-635.
Kiran Maass, Marcel André Fischer, Markus Seiler, Koen Temmerman, Walter Nickel and Matthias Seedorf (2009)
An Intrinsic Quality Control Mechanism Ensures Unconventional Secretion of Fibroblast Growth Factor 2 in a Folded Conformation. J. Cell Sci. 122:3322-3329.
Lucía Cespón Torrado, Koen Temmerman, Hans-Michael Müller, Matthias P. Mayer, Claudia Seelenmeyer, Rafael Backhaus, and Walter Nickel (2009)
Mechanisms of Regulated Unconventional Protein Secretion. Nat. Rev. Mol. Cell Biol. 10:148-155.
Walter Nickel and Catherine Rabouille (2009)
Reversible Phosphorylation as a Molecular Switch to Regulate Plasma Membrane Targeting of Acylated SH4 Domain Proteins. Traffic 10:1047-1060.
Stella Tournaviti, Enrica San Pietro, Stefan Terjung, Tobias Schafmeier, Sabine Wegehingel, Julia Ritzerfeld, Juliane Schulz, Deborah F. Smith, Rainer Pepperkok, and Walter Nickel (2009)
The Golgi-associated Protein p115 Mediates the Secretion of Macrophage Migration Inhibitory Factor. J. Immunol. 182:6896-6906.
Melanie Merk, John Baugh, Swen Zierow, Lin Leng, Utpal Pal, Seung Joon Lee, Antje D. Ebert, Yuka Mizue, John O. Trent, Robert Mitchell, Walter Nickel, Paula B. Kavathas, Jürgen Bernhagen, and Richard Bucala (2009)
Rerouting of Fibroblast Growth Factor 2 to the Classical Secretory Pathway Results in Post-translational Modifications That Block Binding to Heparan Sulfate Proteoglycans. FEBS Lett. 582:2387-2392.
Sabine Wegehingel, Christoph Zehe, and Walter Nickel (2008)
Unconventional Mechanisms of Protein Transport to the Cell Surface of Eukaryotic Cells. Annu. Rev. Cell Dev. Biol. 24:287-308.
Walter Nickel and Matthias Seedorf (2008)
Unconventional Secretion of Fibroblast Growth Factor 2 and Galectin-1 Does Not Require Shedding of Plasma-Membrane-Derived Vesicles. FEBS Lett. 582:1362-1368.
Claudia Seelenmeyer, Carolin Stegmayer, and Walter Nickel (2008)
SH4-domain-induced plasma membrane dynamization promotes bleb-associated cell motility. Journal of cell science, 120(Pt 21), 3820–3829. https://doi.org/10.1242/jcs.011130 Tournaviti, S., Hannemann, S., Terjung, S., Kitzing, T. M., Stegmayer, C., Ritzerfeld, J., Walther, P., Grosse, R., Nickel, W., & Fackler, O. T. (2007)
Unconventional Protein Secretion: An Extracellular Trap For Nonclassical Export of Fibroblast Growth Factor 2. J. Cell Sci. 120:2295-2299.
Walter Nickel (2007)
Cell surface heparan sulfate proteoglycans are essential components of the unconventional export machinery of FGF-2. Proc. Natl. Acad Sci. U.S.A. 103:15479-15484.
Christoph Zehe, André Engling, Sabine Wegehingel, Tobias Schäfer, and Walter Nickel (2006)
Cell Surface Counter Receptors are Essential Components of the Unconventional Export Machinery of Galectin-1. J. Cell Biol. 172:373-381.
Claudia Seelenmeyer, Sabine Wegehingel, Ivo Tews, Markus Künzler, Markus Aebi, and Walter Nickel (2005)
Direct Transport Across the Plasma Membrane of Mammalian Cells of Leishmania HASPB as Revealed by a CHO Export Mutant. J. Cell Sci. 118:517-527.
Carolin Stegmayer, Angelika Kehlenbach, Stella Tournaviti, Sabine Wegehingel, Christoph Zehe, Paul W. Denny, Deborah F. Smith, Blanche Schwappach, and Walter Nickel (2005)
Unconventional Secretory Routes: Direct Protein Export Across the Plasma Membrane of Mammalian Cells. Traffic 6:607-614.
Walter Nickel (2005)
Unconventional Protein Secretion: Membrane Translocation of FGF-2 Does Not Require Protein Unfolding. J. Cell Sci. 117:1727-1736.
Rafael Backhaus, Christoph Zehe, Sabine Wegehingel, Angelika Kehlenbach, Blanche Schwappach, and Walter Nickel (2004)
Unconventional secretion of fibroblast growth factor 2 is mediated by direct translocation across the plasma membrane of mammalian cells. J Biol Chem. 279(8):6244-51. Schäfer T, Zentgraf H, Zehe C, Brügger B, Bernhagen J, Nickel W. (2004)
Functional reconstitution of COPI coat assembly and disassembly using chemically defined components. Proc. Natl. Acad Sci. U.S.A. 100:8253-8257. Constanze Reinhard, Michael Schweikert, Felix T. Wieland, and Walter Nickel (2003)
Regulated secretion of macrophage migration inhibitory factor is mediated by a nonclassical pathway involving an ABC transporter. FEBS Lett. 551:78-86.
Oliver Flieger, André Engling, Richard Bucala, Hongqi Lue, Walter Nickel, and Jürgen Bernhagen (2003)
The Mystery of Non-classical Protein Secretion: A Current View on Cargo Proteins and Potential Export Routes. Eur. J. Biochem. 270:2109-2119.
Walter Nickel (2003)
Biosynthetic FGF-2 is Targeted to Non-Lipid Raft Microdomains Following Translocation to the Extracellular Surface of CHO cells. J. Cell Sci. 115:3619-3631.
André Engling, Rafael Backhaus, Carolin Stegmayer, Christoph Zehe, Claudia Seelenmeyer, Angelika Kehlenbach, Blanche Schwappach, Sabine Wegehingel, and Walter Nickel (2002)
Vesicular transport: the core machinery of COPI recruitment and budding. J Cell Sci. 115(Pt 16):3235-40. Review. Nickel W, Brügger B, Wieland FT. (2002)
Membrane Trafficking: How Transport Vesicles Fuse With Target Membranes in "Protein Modules in Cellular Signalling", eds Heilmeyer L. and Friedrich P. (IOS Press Amsterdam), pp. 257-261 (Review). Walter Nickel, Britta Brügger and Felix T. Wieland (2001)
Molecular Mechanisms of COPI Vesicle Formation in "Protein Modules in Cellular Signalling", eds. Heilmeyer L. and Friedrich P. (IOS Press Amsterdam), pp. 262-267 (Review). Britta Brügger, Walter Nickel, and Felix T. Wieland (2001)
Recruitment to Golgi membranes of ADP-ribosylation factor 1 is mediated by the cytoplasmic domain of p23. The EMBO journal, 20(23), 6751–6760. https://doi.org/10.1093/emboj/20.23.6751 Gommel, D. U., Memon, A. R., Heiss, A., Lottspeich, F., Pfannstiel, J., Lechner, J., Reinhard, C., Helms, J. B., Nickel, W., & Wieland, F. T. (2001)
Allosteric activation of acid a-glucosidase by the human papillomavirus E7 protein. J. Biol. Chem. 275:9534-9541.
Werner Zwerschke, Boris Mannhardt, Paola Massimi, Sonja Nauenburg, David Pim, Walter Nickel, Lawrence Banks, Arnold J. Reuser, Pidder Jansen-Dürr (2000)
Evidence for segregation of sphingomyelin and cholesterol during formation of COPI-coated vesicles. J Cell Biol. 151(3):507-18. Brügger B, Sandhoff R, Wegehingel S, Gorgas K, Malsam J, Helms JB, Lehmann WD, Nickel W, Wieland FT. (2000)
Functional Architecture of Intracellular t-SNAREs: Membrane Fusion by Isolated SNAREs of the Yeast Vacuole. Nature 407:198-202. Ryouichi Fukuda, James A. McNew, Thomas Weber, Francesco Parlati, Thomas Engel, Walter Nickel, James E. Rothman, and Thomas H. Söllner (2000)
Putative fusogenic activity of NSF is restricted to a lipid mixture whose coalescence is also triggered by other factors. EMBO J. 19(6):1272-8. Brügger B, Nickel W, Weber T, Parlati F, McNew JA, Rothman JE, Söllner T. (2000)
Receptor-Dependent Formation of COPI-Coated Vesicles From Chemically Defined Donor Liposomes. Methods Enzymol. 329:388-404. Walter Nickel and Felix T. Wieland (2000)
A role for ADP-ribosylation factor in the control of cargo uptake during COPI-coated vesicle biogenesis. FEBS Lett. 462:267-272. Jörg Malsam, Daniel Gommel, Felix. T. Wieland, and Walter Nickel (1999)
Content mixing and membrane integrity during membrane fusion driven by pairing of isolated v-SNAREs and t-SNAREs. Proc. Natl. Acad Sci. U.S.A. 96 :12571-12576. Walter Nickel, Thomas Weber, James A. McNew, Francesco Parlati, Thomas H. Söllner, and James E. Rothman (1999)
COPI-Mediated Protein and Lipid Sorting. Protoplasma 207:115-124 (Review). Walter Nickel and Britta Brügger (1999)
Coupling of coat assembly and vesicle budding to packaging of putative cargo receptors. Cell 96, 495-506. M. Bremser, W. Nickel, M. Schweikert, M. Ravazzola, M. Amherd, C.A. Hughes, T.H. Söllner, J. E. Rothman, and F. T. Wieland (1999)
p24 and p23, the major transmem-brane proteins of COPI-coated transport vesicles, form hetero-oligomeric complexes and cycle between the organelles of the early secretory pathway. FEBS Lett. 447:179-185. D. Gommel, L. Orci, E.M. Emig, M.J. Hannah, M. Ravazzola, W. Nickel, J.B. Helms, F.T. Wieland and K. Sohn (1999)
A putative heterotrimeric G protein inhibits the fusion of COPI-coated vesicles. Segregation of heterotrimeric G proteins from COPI-coated vesicles. J Biol Chem. 273(24):15203-8. Helms JB, Helms-Brons D, Brügger B, Gkantiragas I, Eberle H, Nickel W, Nürnberg B, Gerdes HH, Wieland FT. (1998)
Biosynthetic Protein Transport Through the Early Secretory Pathway. Histochem. Cell Biol. 109:477-486 (Review). Walter Nickel and Felix T. Wieland (1998)
Intracellular Transport of Glycoproteins and Glycolipids. Trends Glycosci. Glycotechnolog. 10:1-11 (Review). Walter Nickel, Britta Brügger, and Felix T. Wieland (1998)
Protein and lipid sorting between the endoplasmic reticulum and the Golgi complex. Semin Cell Dev Biol. 9(5):493-501. Review. Nickel W, Brügger B, Wieland FT. (1998)
Uptake by COPI-coated vesicles of both anterograde and retrograde cargo is inhibited by GTPgammaS in vitro. J. Cell Sci. 111:3081-3090. Walter Nickel, Jörg Malsam, Karin Gorgas, Mariella Ravazzola, Nicole Jenne, J. Bernd Helms, and Felix T. Wieland (1998)
Biogenesis of COPI-Coated Transport Vesicles. FEBS Lett. 413:395-400 (Review). Walter Nickel and Felix T. Wieland (1997)
p23, a major COPI-vesicle membrane protein, constitutively cycles through the early secretory pathway. Proc. Natl. Acad. Sci. U.S.A. 94, 11393-11398. W. Nickel, K. Sohn, C. Bünning, and F. Wieland (1997)
Protein-Reifung: Transport, Faltung und Abbau. Biospektrum 4: 22-24 (Review).
Walter Nickel and Klaus Leitzgen (1997)
Forskolin stimulates detoxification of brefeldin A. J. Biol. Chem. 271:15870-15873. Walter Nickel, J. Bernd Helms, Richard E. Kneusel, and Felix T. Wieland (1996)
Sorting and budding of constitutive secretory vesicles in hepatocytes and hepatoma cells. Adv. Enzyme Regul. 35:283-292.
Andreas Barthel, Walter Nickel, Christiane Tonko, and Hans-Dieter Söling (1995)
ADP-ribosylation factor (ARF) and a 14 kDa Polypeptide Are Associated With Heparan Sulfate Proteoglycan-carrying Post-trans-Golgi network Secretory Vesicles. J. Cell Biol. 125:721-731.
Walter Nickel, Lukas A. Huber, Richard A. Kahn, Nicola Kipper, Andreas Barthel, Dirk Faßhauer, and Hans-Dieter Söling (1994)
ARF and VAPP14: Two Proteins Involved in the Delivery of Heparan Sulfate Proteoglycan From the TGN to the Cell Surface. Ann. NY Acad. Sci. 1994:344-356.
Walter Nickel, Richard A. Kahn, Nicola Kipper, Andreas Barthel, Dirk Faßhauer, and Hans-Dieter Söling (1994)
Funktionelle und strukturelle Untersuchungen zum vesikulären Golgi-Plasmamembran-Transport in Leberzellen. PhD thesis. Georg-August-Universität Göttingen. ©Cuvillier-Verlag Göttingen.
Walter Nickel (1994)
Interactions of Azidothymidine Triphosphate with the Cellular DNA Polymerases alpha, delta and epsilon and with DNA Primase. J. Biol. Chem. 267:848-854.
Walter Nickel, Sabine Austermann, Gabriele Bialek, and Frank Grosse (1992)
Collaborations
Rainer Pepperkok, EMBL Heidelberg
Holger Erfle, Bioquant Heidelberg
Matthias Mayer, ZMBH Heidelberg
Joe Lewis and David Will, EMBL Heidelberg
Petr Chlanda, BioQuant Heidelberg
Christian Freund, FU Berlin
Helge Ewers, FU Berlin
Frank Noé, FU Berlin
Ünal Coskun, Dresden
Alf Honigmann, Dresden
Ana Garcia-Saez, Tübingen
Martin Hof, Prague
Ilpo Vattulainen, Helsinki
Coordinating functions
Coordinating functions:
2021-
Managing Director of Heidelberg University Biochemistry Center
2019-
Dean of studies of the Bachelor and Master programmes in Biochemistry (Faculty of Biosciences, Heidelberg University)
2016-
Speaker and founding chair of the DFG Collaborative Research Centre SFB/TRR 186 Heidelberg/Berlin; "Molecular switches in the spatio-temporal control of cellular sognal transmission"
2011-2014
Chair of the DFG Graduate School "Quantitative Analysis of Dynamic Processes in
Membrane Transport and Translocation" (GRK 1188)
2009-2012
Chair of the EuroMembrane Programme of the European Science Foundation (ESF)
2005-2010
Vice-Chair of the DFG Graduate School "Quantitative Analysis of Dynamic Processes in Membrane Transport and Translocation" (GRK 1188)
Funding
Past and current funding of our laboratory came from the German Research Foundation (DFG), the European Science Foundation (ESF), the Federal Ministry of Education and Research (BMBF), the Baden-Württemberg Foundation, the Peter and Traudl Engelhorn Foundation and the Boehringer Ingelheim Fonds (BIF).
Contact
Heidelberg University
Biochemistry Center (BZH)
Im Neuenheimer Feld 328
69120 Heidelberg
Biochemistry Center (BZH)
Im Neuenheimer Feld 328
69120 Heidelberg
Office:
+49 6221 54-5425 Lab:
+49 6221 54-5427 Fax:
+49 6221 54-4366 E-Mail:
walter.nickel@bzh.uni-heidelberg.de