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.
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
Download BZH Report Nickel 2014-2016
CV
| 2004 | Professor of Biochemistry at Heidelberg University Biochemistry Center (BZH) Faculty of Biosciences |
| 2001 | 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 |
| 2021- | Managing Director of the Heidelberg University Biochemistry Center (BZH) |
Lab Members
From left to right: Cyril Legrand (PhD Student), Annalena Meyer (PhD Student), Alina Muschko (PhD Student), Amazir Bredl (Biochemistry Bachelor Student), Daniel Beyer (PhD Student), Hans-Michael Müller (Senior Postdoc), Walter Nickel, Sabine Wegehingel (Technical Assistant), Carola Sparn (PhD Student), Roberto Saleppico (PhD Student) and Fabio Lolicato (Postdoc). Not on this picture: Julia Steringer (Postdoc)
Daniel Beyer
PhD student
PhD student
Lab:Room 323
/ Phone: +49 6221 54-4746
Mail:daniel.beyer@bzh.uni-heidelberg.de
Maximilian Bullemer
research assistant
research assistant
Lab:Room 305
/ Phone: +49 6221 54-4351
Mail:bullemer@stud.uni-heidelberg.de
Jaime Fernandez Sobaberas
PhD student
PhD student
Lab:Room 322
/ Phone: +49 6221 54-5428
Mail:jaime.fernandez-sobaberas@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
Carola Sparn
PhD student
PhD student
Lab:Room 322
/ Phone: +49 6221 54-5428
Mail:carola.sparn@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
Walter Nickel in PubMed
Selected original publications:
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-Saéz 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 Rep 23:2039-2055
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)
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) Small Molecule Inhibitors Targeting Tec Kinase Block Unconventional Secretion of Fibroblast Growth Factor 2. J. Biol. Chem. 291:17787-803
Zeitler M, Steringer JP, Müller HM, Mayer MP, Nickel W (2015) HIV-Tat Forms Phosphoinositide Dependent Membrane Pores Implicated in Unconventional Protein Secretion. J. Biol. Chem. 290:21976-84
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
Zacherl S, La Venuta G, Müller HM, Wegehingel S, Dimou E, Sehr P, Lewis JD, Erfle H, Pepperkok R, Nickel W (2014) A direct role for ATP1A1 in unconventional secretion of fibroblast growth factor 2. J. Biol. Chem. 290:3654-3665
Steringer, JP, Bleicken, S, Andreas, H, Zacherl, S, Laussmann, M, Temmerman, K, Contreras, FX, Bharat, TA, Lechner, J, Müller, HM, Briggs, JA, Garcia, AJ, Nickel, W (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. J. Biol. Chem. 2012; 287(33):27659-69.
Antje Ebert, Mareike Laußmann, Sabine Wegehingel, Lars Kaderali, Holger Erfle, Jürgen Reichert, Johannes Lechner, Hans-Dietmar Beer, Rainer Pepperkok and Walter Nickel (2010) Tec kinase mediated phosphorylation of Fibroblast Growth Factor 2 is essential for unconventional secretion. Traffic 11:813-826
Lucía Cespón Torrado, Koen Temmerman, Hans-Michael Müller, Matthias P. Mayer, Claudia Seelenmeyer, Rafael Backhaus, and Walter Nickel (2009) An Intrinsic Quality Control Mechanism Ensures Unconventional Secretion of Fibroblast Growth Factor 2 in a Folded Conformation. J. Cell Sci. 122:3322-3329
Koen Temmerman, Antje D. Ebert, Hans-Michael Müller, Irmgard Sinning, Ivo Tews, and Walter Nickel (2008) A Direct Role for Phosphatidylinositol-4,5-bisphosphate in Unconventional Secretion of Fibroblast Growth Factor 2. Traffic 9:1204-1217
Christoph Zehe, André Engling, Sabine Wegehingel, Tobias Schäfer, and Walter Nickel (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
Claudia Seelenmeyer, Sabine Wegehingel, Ivo Tews, Markus Künzler, Markus Aebi, and Walter Nickel (2005) Cell Surface Counter Receptors are Essential Components of the Unconventional Export Machinery of Galectin-1. J. Cell Biol. 172:373-381
Tobias Schäfer, Hanswalter Zentgraf, Christoph Zehe, Britta Brügger, Jürgen Bernhagen, and Walter Nickel (2004) Unconventional Protein Secretion of Fibroblast Growth Factor 2 Is Mediated by Direct Translocation across the Plasma Membrane of Mammalian Cells. J. Biol. Chem. 279:6244-6251
Selected review articles:
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
Steringer JP and Nickel W (2018) A direct gateway into the extracellular space: Unconventional secretion of FGF2 through self-sustained plasma membrane pores. Sem Cell Dev Biol, PMID:29458182
Brough D, Pellegrin P, and Nickel W (2017) 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; PMID:28871048
La Venuta G, Zeitler M, Steringer JP, Müller HM, 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. 290:27015-20
Steringer JP, Müller HM, Nickel W (2014) Unconventional Secretion of Fibroblast Growth Factor 2-A Novel Type of Protein Translocation across Membranes? J. Mol. Biol. 427:1202-1210
Rabouille C, Malhotra V, Nickel W. (2012) Diversity in unconventional protein secretion.
J Cell Sci. 125:5251-5.
Walter Nickel (2011) The Unconventional Secretory Machinery of Fibroblast Growth Factor 2. Traffic 12:799-805
Walter Nickel and Catherine Rabouille (2009) Mechanisms of Regulated Unconventional Protein Secretion. Nat. Rev. Mol. Cell Biol. 10:148-155
Walter Nickel and Matthias Seedorf (2008) Unconventional Mechanisms of Protein Transport to the Cell Surface of Eukaryotic Cells. Annu. Rev. Cell Dev. Biol. 24:287-308
Complete list of publications
2020
Sachl R, Cujova S, Singh V, Riegerova P, Kapusta P, Müller HM, Steringer JP, Hof M and Nickel W (2020) Functional assay to correlate protein oligomerization states with membrane pore formation. Anal Chem 92(22):14861-14866
Pallotta MT and Nickel W (2020) FGF2 and IL-1β: Explorers of unconventional secrtory pathways.
J Cell Sci 133(21):jcs250449
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
2019
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) Single event visualization of unconventional secretion of FGF2. J Cell Biol 218:683-699
Ahmed M, Legrand C, Yagüe Relimpio A, Beretta CA, Muschko A, Wegehingel S, Müller HM, Sehr P, Will DW, Lewis JD, Nickel W (2019) A time-resolved live cell imaging assay to identify small molecule inhibitors of FGF2 signaling. FEBS Lett. 593:2162-2176
2018
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 Rep 23:2039-2055
Dimou E and Nickel W (2018) Unconventional mechanisms of eukaryotic protein secretion.
Curr Biol 28:R406-R410
Nickel W and Rabouille C (2018) Unconventional protein secretion: Diversity and consensus.
Sem Cell Dev Biol, PMID:29549063
Steringer JP and Nickel W (2018) The molecular mechanism underlying unconventional secretion of Fibroblast Growth Factor 2 from tumour cells. Sem Cell Dev Biol, PMID:29458182
2017
Brough D, Pellegrin P, and Nickel W (2017) 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
Steringer JP and Nickel W (2017) The molecular mechanism underlying unconventional secretion of fibroblast growth factor 2 from tumor cells. Biol. Cell 109:375-380
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)
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) 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
2016
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) Small Molecule Inhibitors Targeting Tec Kinase Block Unconventional Secretion of Fibroblast Growth Factor 2. J. Biol. Chem. 291:17787-803
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) Inflammasome-dependent IL-1β release depends upon membrane permeabilisation. Cell Death Differ. 23:1219-31
Gerl MJ, Bittl V, Kirchner S, Sachsenheimer T, Brunner HL, Lüchtenborg C, Özbalci C, Wiedemann H, Wegehingel S, Nickel W, Haberkant P, Schultz C, Krüger M, Brügger B. (2016) Sphingosine-1-Phosphate Lyase Deficient Cells as a Tool to Study Protein Lipid Interactions. PLoS One 11:e0153009
2015
La Venuta G, Zeitler M, Steringer JP, Müller HM, 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]
Zeitler M, Steringer JP, Müller HM, Mayer MP, Nickel W (2015)
HIV-Tat Forms Phosphoinositide Dependent Membrane Pores Implicated in Unconventional Protein Secretion. J Biol Chem [Epub ahead of print]
Stiess M, Wegehingel S, Nguyen C, Nickel W, Bradke F, Cambridge SB (2015)
A Dual SILAC Proteomic Labeling Strategy for Quantifying Constitutive and Cell-Cell Induced Protein Secretion.
J Proteome Res [Epub ahead of print]
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.
2014
Zacherl S, La Venuta G, Müller HM, Wegehingel S, Dimou E, Sehr P, Lewis JD, Erfle H, Pepperkok R, Nickel W (2014) A direct role for ATP1A1 in unconventional secretion of fibroblast growth factor 2. J. Biol. Chem. 290:3654-3665
Ugarte-Uribe B, Müller HM, Otsuki M, Nickel W, García-Sáez AJ. (2014) Dynamin-related protein 1 (Drp1) promotes structural intermediates of membrane division. J. Biol. Chem. 289:30645-30656
Steringer JP, Müller HM, Nickel W (2014) Unconventional Secretion of Fibroblast Growth Factor 2-A Novel Type of Protein Translocation across Membranes? J. Mol. Biol. 427:1202-1210
Geist MM, Pan X, Bender S, Bartenschlager R, Nickel W, Fackler OT. (2014) Heterologous Src homology 4 domains support membrane anchoring and biological activity of HIV-1 Nef.
J. Biol. Chem. 289:14030-14044
2013
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) CDC42 switches IRSp53 from inhibition of actin growth to elongation by clustering of VASP. EMBO J. 32:2735-50
Bhardwaj R, Müller HM, Nickel W, Seedorf M. (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)
Di Ventura B, Knecht B, Andreas H, Godinez WJ, Fritsche M, Rohr K, Nickel W, Heermann DW, Sourjik V. (2013) Chromosome segregation by the Escherichia coli Min system.
Mol Syst Biol. 2013;9:686
Pan X, Geist MM, Rudolph JM, Nickel W, Fackler OT (2013) HIV-1 Nef disrupts membrane- microdomain-associated anterograde transport for plasma membrane delivery of selected Src family kinases. Cell Microbiol. 15:1605-21
Ernst AM, Zacherl S, Herrmann A, Hacke M, Nickel W, Wieland FT, Brügger B. (2013) Differential Transport of Influenza A Neurominidase Signal Anchor Peptides to the Plasma Membrane. FEBS Lett. 587:1411-7
2012
Rabouille C, Malhotra V, Nickel W. (2012) Diversity in unconventional protein secretion.
J Cell Sci. 125:5251-5.
Steringer, JP, Bleicken, S, Andreas, H, Zacherl, S, Laussmann, M, Temmerman, K, Contreras, FX, Bharat, TA, Lechner, J, Müller, HM, Briggs, JA, Garcia, AJ, Nickel, W (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. J Biol Chem. 287:27659-69.
Maclean, LM, O'Toole, PJ, Stark, M, Marrison, J, Seelenmeyer, C, Nickel, W, and Smith, DF (2012) Trafficking and release of Leishmania metacyclic HASPB on macrophage invasion. Cell Microbiol. 14:740-761
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) Loss of ceramide synthase 3 causes lethal skin barrier disruption. Hum Mol Genet. 21:586-608
2011
Julia Ritzerfeld, Steffen Remmele, Tao Wang, Koen Temmerman, Britta Brügger, Sabine Wegehingel, Stella Tournaviti, Jeroen R.P.M. Strating, Felix T. Wieland, Beate Neumann, Jan Ellenberg, Chris Lawerenz, Jürgen Hesser, Holger Erfle, Rainer Pepperkok, and Walter Nickel (2011) Phenotypic Profiling of the Human Genome Reveals Gene Products Involved in Plasma Membrane Targeting of SRC Kinases. Genome Res. 21:1955-1968
Thomas Kupke, Leontina Di Cecco, Hans-Michael Müller, Annett Neuner, Frank Adolf, Felix Wieland, Walter Nickel and Elmar Schiebel (2011) Targeting of Nbp1 to the inner nuclear membrane is essential for SPB duplication. EMBO J. 30:3337-3352
Walter Nickel (2011) The Unconventional Secretory Machinery of Fibroblast Growth Factor 2. Traffic 12:799-805
2010
Walter Nickel (2010) Pathways of Unconventional Protein Secretion. Curr. Opin. Biotechnol. 21:621-626
Antje Ebert, Mareike Laußmann, Sabine Wegehingel, Lars Kaderali, Holger Erfle, Jürgen Reichert, Johannes Lechner, Hans-Dietmar Beer, Rainer Pepperkok and Walter Nickel (2010) Tec kinase mediated phosphorylation of Fibroblast Growth Factor 2 is essential for unconventional secretion. Traffic 11:813-826
2009
Ebru Ercan, Frank Momburg, Ulrike Engel, Koen Temmerman, Walter Nickel and Matthias Seedorf (2009) 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
Lucía Cespón Torrado, Koen Temmerman, Hans-Michael Müller, Matthias P. Mayer, Claudia Seelenmeyer, Rafael Backhaus, and Walter Nickel (2009) An Intrinsic Quality Control Mechanism Ensures Unconventional Secretion of Fibroblast Growth Factor 2 in a Folded Conformation. J. Cell Sci. 122:3322-3329
Stella Tournaviti, Enrica San Pietro, Stefan Terjung, Tobias Schafmeier, Sabine Wegehingel, Julia Ritzerfeld, Juliane Schulz, Deborah F. Smith, Rainer Pepperkok, and Walter Nickel (2009) Reversible Phosphorylation as a Molecular Switch to Regulate Plasma Membrane Targeting of Acylated SH4 Domain Proteins. Traffic 10:1047-1060
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) The Golgi-associated Protein p115 Mediates the Secretion of Macrophage Migration Inhibitory Factor. J. Immunol. 182:6896-6906
Marcel A. Fischer, 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
Koen Temmerman and Walter Nickel (2009) A novel flow cytometric assay to quantify interactions between proteins and membrane lipids. J. Lipid Res. 50:1245-1254
Kiran Maass, Marcel André Fischer, Markus Seiler, Koen Temmerman, Walter Nickel and Matthias Seedorf (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
Walter Nickel and Catherine Rabouille (2009) Mechanisms of Regulated Unconventional Protein Secretion. Nat. Rev. Mol. Cell Biol. 10:148-155
2008
Walter Nickel and Matthias Seedorf (2008) Unconventional Mechanisms of Protein Transport to the Cell Surface of Eukaryotic Cells. Annu. Rev. Cell Dev. Biol. 24:287-308
Sabine Wegehingel, Christoph Zehe, and Walter Nickel (2008) 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
Koen Temmerman, Antje D. Ebert, Hans-Michael Müller, Irmgard Sinning, Ivo Tews, and Walter Nickel (2008) A Direct Role for Phosphatidylinositol-4,5-bisphosphate in Unconventional Secretion of Fibroblast Growth Factor 2. Traffic 9:1204-1217
Claudia Seelenmeyer, Carolin Stegmayer, and Walter Nickel (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
2007
Walter Nickel (2007) Unconventional Protein Secretion: An Extracellular Trap For Nonclassical Export of Fibroblast Growth Factor 2. J. Cell Sci. 120:2295-2299
Tournaviti S, Hannemann S, Terjung S, Kitzing TM, Stegmayer C, Ritzerfeld J, Walther P, Grosse R, Nickel W, Fackler OT. SH4-domain-induced plasma membrane dynamization promotes bleb-associated cell motility.
J Cell Sci. 2007, 120 (Pt 21):3820-9.
2006
Christoph Zehe, André Engling, Sabine Wegehingel, Tobias Schäfer, and Walter Nickel (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
2005
Claudia Seelenmeyer, Sabine Wegehingel, Ivo Tews, Markus Künzler, Markus Aebi, and Walter Nickel (2005) Cell Surface Counter Receptors are Essential Components of the Unconventional Export Machinery of Galectin-1. J. Cell Biol. 172:373-381
Walter Nickel (2005) Unconventional Secretory Routes: Direct Protein Export Across the Plasma Membrane of Mammalian Cells. Traffic 6:607-614
Carolin Stegmayer, Angelika Kehlenbach, Stella Tournaviti, Sabine Wegehingel, Christoph Zehe, Paul W. Denny, Deborah F. Smith, Blanche Schwappach, 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
2004
Rafael Backhaus, Christoph Zehe, Sabine Wegehingel, Angelika Kehlenbach, Blanche Schwappach, and Walter Nickel (2004) Unconventional Protein Secretion: Membrane Translocation of FGF-2 Does Not Require Protein Unfolding. J. Cell Sci. 117:1727-1736
Tobias Schäfer, Hanswalter Zentgraf, Christoph Zehe, Britta Brügger, Jürgen Bernhagen, and Walter Nickel (2004) Unconventional Protein Secretion of Fibroblast Growth Factor 2 Is Mediated by Direct Translocation across the Plasma Membrane of Mammalian Cells. J. Biol. Chem. 279:6244-6251
2003
Oliver Flieger, André Engling, Richard Bucala, Hongqi Lue, Walter Nickel, and Jürgen Bernhagen (2003) Regulated secretion of macrophage migration inhibitory factor is mediated by a nonclassical pathway involving an ABC transporter. FEBS Lett. 551:78-86
Constanze Reinhard, Michael Schweikert, Felix T. Wieland, and Walter Nickel (2003) Functional reconstitution of COPI coat assembly and disassembly using chemically defined components. Proc. Natl. Acad Sci. U.S.A. 100:8253-8257
Walter Nickel (2003) The Mystery of Non-classical Protein Secretion: A Current View on Cargo Proteins and Potential Export Routes.
Eur. J. Biochem. 270:2109-2119
Claudia Seelenmeyer, Sabine Wegehingel, Johannes Lechner, and Walter Nickel (2003) The tumor antigen CA125 represents a novel counter receptor for galectin-1. J. Cell Sci. 116:1305-1318
2002
André Engling, Rafael Backhaus, Carolin Stegmayer, Christoph Zehe, Claudia Seelenmeyer, Angelika Kehlenbach, Blanche Schwappach, Sabine Wegehingel, and Walter Nickel (2002) 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
Walter Nickel, Britta Brügger, and Felix T. Wieland (2002) Vesicular Transport: the Core Machinery of COPI recruitment and budding. J. Cell Sci. 115:3235-3240 (Review)
2001
Daniel U.Gommel, Abdul R. Memon, Armin Heiss, Friedrich Lottspeich, Constanze Reinhard, J. Bernd Helms, Walter Nickel, and Felix T. Wieland (2001) Recruitment to Golgi Membranes of ADP-Ribosylation Factor 1 is Mediated by the Cytoplasmic Domain of p23. EMBO J. 20:6751-6760
Walter Nickel, Britta Brügger and Felix T. Wieland (2001) 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)
Britta Brügger, Walter Nickel, 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) Sorting Into COPI Vesicles of Protein and Lipid Cargo in "Protein Modules in Cellular Signalling", eds. Heilmeyer L. and Friedrich P. (IOS Press Amsterdam), pp. 268-275 (Review)
2000
Walter Nickel and Felix T. Wieland (2000) Receptor-Dependent Formation of COPI-Coated Vesicles From Chemically Defined Donor Liposomes. Methods Enzymol. 329:388-404
Britta Brügger, Roger Sandhoff, J.Bernd Helms, Karin Gorgas, Wolf D. Lehmann, Walter Nickel, F.T. Wieland (2000) Segregation from COPI-Coated Vesicles of Sphingomyelin and Cholesterol. J. Cell Biol. 151:507-518
Ryouichi Fukuda, James A. McNew, Thomas Weber, Francesco Parlati, Thomas Engel, Walter Nickel, James E. Rothman, and Thomas H. Söllner (2000) Functional Architecture of Intracellular t-SNAREs: Membrane Fusion by Isolated SNAREs of the Yeast Vacuole. Nature 407:198-202
Britta Brügger, Walter Nickel, Thomas Weber, Frank Parlati, James A. McNew, James E. Rothman, and Thomas H. Söllner (2000) Putative Fusogenic Activity of NSF is Restricted to Lipid Mixtures Whose Coalescence is Also Triggered by Other Factors. EMBO J. 19:1272-1278
Werner Zwerschke, Boris Mannhardt, Paola Massimi, Sonja Nauenburg, David Pim, Walter Nickel, Lawrence Banks, Arnold J. Reuser, Pidder Jansen-Dürr (2000) Allosteric activation of acid a-glucosidase by the human papillomavirus E7 protein. J. Biol. Chem. 275:9534-9541
1999
Jörg Malsam, Daniel Gommel, Felix. T. Wieland, and Walter Nickel (1999) A role for ADP-ribosylation factor in the control of cargo uptake during COPI-coated vesicle biogenesis. FEBS Lett. 462:267-272.
Walter Nickel, Thomas Weber, James A. McNew, Francesco Parlati, Thomas H. Söllner, and James E. Rothman (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.
D. Gommel, L. Orci, E.M. Emig, M.J. Hannah, M. Ravazzola, W. Nickel, J.B. Helms, F.T. Wieland and K. Sohn (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.
Walter Nickel and Britta Brügger (1999) COPI-Mediated Protein and Lipid Sorting. Protoplasma 207:115-124 (Review)
Martina Bremser*, Walter Nickel*, Michael Schweikert, Mariella Ravazzola, Mylène Amherdt, Christine A. Hughes, Thomas H. Söllner, James E. Rothman, and Felix T. Wieland (1999) Coupling of Coat Assembly and Vesicle Budding to Packaging of Putative Cargo Receptors. Cell 96:495-506 *first authors
1998
Walter Nickel, Britta Brügger, and Felix T. Wieland (1998) Protein and Lipid Sorting Between the Endoplasmic Reticulum and the Golgi Complex. Sem. Cell Dev. Biol. 9:493-501. (Review)
Walter Nickel, Jörg Malsam, Karin Gorgas, Mariella Ravazzola, Nicole Jenne, J. Bernd Helms, and Felix T. Wieland (1998) Uptake by COPI-coated Vesicles of Both Anterograde and Retrograde Cargo Molecules is Inhibited by GTPgS In Vitro. J. Cell Sci. 111:3081-3090.
J. Bernd Helms, Desire Helms-Brons, Britta Brügger, Ioannis Gkantiragas, Heike Eberle, Walter Nickel, Bernd Nürnberg, Hans-Hermann Gerdes, and Felix T. Wieland (1998) A Putative Heterotrimeric G Protein Inhibits the Fusion of COPI-coated Vesicles. J. Biol. Chem. 273:15203-15208.
Walter Nickel, Britta Brügger, and Felix T. Wieland (1998) Intracellular Transport of Glycoproteins and Glycolipids. Trends Glycosci. Glycotechnolog. 10:1-11 (Review)
Walter Nickel and Felix T. Wieland (1998) Biosynthetic Protein Transport Through the Early Secretory Pathway. Histochem. Cell Biol. 109:477-486. (Review)
1997
Walter Nickel and Felix T. Wieland (1997) Biogenesis of COPI-Coated Transport Vesicles. FEBS Lett. 413:395-400 (Review)
Walter Nickel, Kai Sohn, Carsten Bünning, 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.
Walter Nickel and Klaus Leitzgen (1997) Protein-Reifung: Transport, Faltung und Abbau. Biospektrum 4: 22-24 (Review)
1996
Walter Nickel, J. Bernd Helms, Richard E. Kneusel, and Felix T. Wieland (1996) Forskolin stimulates detoxification of brefeldin A. J. Biol. Chem. 271:15870-15873.
1995
Andreas Barthel, Walter Nickel, Christiane Tonko, and Hans-Dieter Söling (1995) Sorting and budding of constitutive secretory vesicles in hepatocytes and hepatoma cells. Adv. Enzyme Regul. 35:283-292
1994
Walter Nickel, 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, Lukas A. Huber, Richard A. Kahn, Nicola Kipper, Andreas Barthel, Dirk Faßhauer, and Hans-Dieter Söling (1994) 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 (1994) Funktionelle und strukturelle Untersuchungen zum vesikulären Golgi-Plasmamembran-Transport in Leberzellen. PhD thesis. Georg-August-Universität Göttingen. ©Cuvillier-Verlag Göttingen
1992
Walter Nickel, Sabine Austermann, Gabriele Bialek, and Frank Grosse (1992) Interactions of Azidothymidine Triphosphate with the Cellular DNA Polymerases alpha, delta and epsilon and with DNA Primase. J. Biol. Chem. 267:848-854
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:
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