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Groupleader: Felix Wieland

Vesicular Transport, Protein-Lipid Interactions 

Group Leader Felix Wieland

Felix Wieland

Vesicular Transport, Protein-Lipid Interactions

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Research 


Our research interests comprise two converging fields:

i) Molecular mechanisms of coated vesicle formation,

and

ii) Specificity and structural basis for protein-lipid interactions within the bilayer,
in collaboration with Prof. Britta Brügger





 

i) Molecular mechanisms of coated vesicle formation
 



 
In the eukaryotic cell, vesicular transport represents the basic mechanism for i) maintaining the homeostasis of the endomembrane system, ii) biosynthetic transport of newly synthesized proteins and lipids, and iii) the uptake and intracellular transport of exogenous macromolecules. Three classes of coated vesicles are well established to mediate transport in the exo- and endocytic pathway: COPII vesicles for ER export, COPI vesicles for retrograde Golgi-ER and bidirectional intra-Golgi transport, and clathrin-coated vesicles operating in the late secretory and endocytic pathway. Coat components are involved in multiple tasks such as cargo selection, curvature formation at the donor membrane, vesicle fission and initiation of uncoating.

We are interested in the molecular mechanisms underlying intracellular transport by COPI coated vesicles. In contrast to COPII and clathrin coats, the heptameric large COPI coat component coatomer is recruited en bloc to the membrane, so that both the inner and outer shell of the vesicle are formed at the same time. Recently, the two coatomer subunits γ-COP and ζ-COP were found to exist in two isoforms. Each isoform is, like all other subunits, present in coatomer as one copy, resulting in four possible different heptameric protein complexes. We found that these coatomer isoforms localize differentially within the Golgi of mammalian cells, suggesting different sites of budding for each of them.
In our view, the formation of a COPI transport vesicle involves the following minimal set of components:  donor membranes with transmembrane proteins acting as coat and/or cargo receptors (e.g. members of the p24 family), cytosolic Arf1, cytosolic coatomer and auxiliary enzymes that serve as nucleotide exchange factors for activation on the membrane of Arf1 (GBF1) and GTPase activating proteins for the activation of GTP hydrolysis by Arf1 (Arf GAPs).
We are studying the cooperation of these proteins in the formation of the COPI coat and in the scission of COPI coated buds with a wide range of methods in Biochemistry, Molecular Biology, Cell Biology and Biophysics.
In collaboration with John Briggs’ and Irmi Sinning’s groups we are interested in the structure of the coat protein coatomer as a monomeric, soluble complex, as well as in its membrane bound form as a coating network.

Our present view of the molecular mechanisms underlying the process of budding are depicted in the figure above.
Collaborations with:          
James E. Rothman, Yale                            
                                       Graham Warren, Vienna,
                                       Rainer Pepperkok, EMBL Heidelberg
                                       John Briggs, EMBL Heidelberg
                                       Irmi Sinning, BZH, Heidelberg


Selected publications on Molecular mechanisms of coated vesicle formation:
F. Wieland, M. Gleason, T. Serafini, J. Rothman (1987) The Rate of Bulk Flow from the Endoplasmic Reticulum to the Cell Surface. Cell 50, 289-300.

M. R. Block, B. S. Glick, C. A. Wilcox, F. Wieland, and J. Rothman (1988) Purification of an N-Ethylmaleimide-Sensitive Protein Catalyzing Vesicular Transport. Proc. Natl. Acad. Sci.U.S.A. 85, 7852-7856.

A. Karrenbauer, D. Jeckel. W. Just, R. Birk, R. R. Schmidt, J. E. Rothman, and F. Wieland (1990) The Rate of Bulk Flow from the Golgi to the Plasma Membrane. Cell 63, 259-267.

T. Serafini, G. Stenbeck, A. Brecht, F. Lottspeich, L. Orci, J. E. Rothman, and F. Wieland (1991) A Coat Subunit of Golgi-Derived non-Clathrin Coated Vesicles with Homology to the Clathrin Coated Vesicle Coat Protein b-Adaptin. Nature 349, 215-220.

G. Stenbeck, C. Harter, A. Brecht, D. Herrmann, F. Lottspeich, L. Orci, and F. T. Wieland (1993) b'-COP, a Novel Subunit of Coatomer. EMBO J. 12, 2841-2845.

J. E. Rothman and F. T. Wieland  (1996) Protein sorting by transport vesicles. Science 272, 227-234.

K. Sohn, L. Orci, M. Ravazzola, M. Amherdt, M. Bremser, F. Lottspeich, K. Fiedler, J. B. Helms, and F. Wieland (1996) A major transmembrane protein of Golgi-derived COPI-coated vesicles involved in coatomer binding. J. Cell Biol. 135, 1238-1248.

C. Reinhard, C. Harter, M. Bremser, B. Brügger, K. Sohn. B. Helms, and F. Wieland (1999) Receptor induced polymerisation of coatomer. Proc. Natl. Acad. Sci. U.S.A. 96, 1224-1228.

M. Bremser, W. Nickel, M. Schweikert, M. Ravazzola, M. Amherd, C.A. Hughes, T.H. Söllner, J. E. Rothman, and F. T. Wieland (1999) Coupling of coat assembly and vesicle budding to packaging of putative cargo receptors. Cell 96, 495-506.

D. Gommel, A. R. Memon, A. Heiss, F. Lottspeich, J. Pfannstiel, J. Lechner, C. Reinhard, J. B. Helms, W. Nickel, F. T. Wieland (2001) Recruitment to Golgi Membranes of ADP-Ribosylation Factor is mediated by the cytoplasmic domain of p23, EMBO J. 20, 6751-6760.

C. Reinhard, M. Schweikert, F.T. Wieland, W. Nickel (2003) Functional reconstitution of COPI coat assembly and disassembly using chemically defined components. Proc. Natl. Acad. Sci. USA 100, 8253-8257.

D. Wegmann, P. Hess, C. Baier, F. T. Wieland and C. Reinhard (2004). Novel isotypic g/z-subunits reveal three coatomer complexes in mammals. Mol. Cell. Biol. 24, 1070-1080.

J. Moelleken, J. Malsam, M.J. Betts, A. Movafeghi, I. Reckmann, I. Meissner, A. Hellwig, R.B. Russell, T. Söllner, B. Brügger and F. Wieland (2007): Differential localization of coatomer complex isoforms within the Golgi apparatus. Proc. Natl. Acad. Sci. USA, 104: 4425-4430.

R. Beck, Z. Sun, F. Adolf, C. Rutz, J. Bassler, K. Wild, I. Sinning, E. Hurt, B. Brügger, J. Béthune*, and F. Wieland* (2008) Membrane curvature induced by Arf1-GTP is essential for vesicle formation. Proc.Natl.Acad.Sci.USA, 105:11731-6.

R. Beck, S. Prinz, P. Diestelkötter-Bachert, S. Röhling, F. Adolf, K. Hoehner, S. Welsch, P. Ronchi, B. Brügger, J.A. Briggs, and F. Wieland (2011) Coatomer and dimeric ADP ribosylation factor 1 (Arf1) promote distinct steps in membrane scission. J Cell Biol. 194(5):765-77.

M. Faini, S. Prinz, R. Beck, M. Schorb, J.D. Riches, K. Bacia, B. Brügger, F.T. Wieland & J.A.G. Briggs (2012). The Structures of COPI-Coated Vesicles Reveal Alternate Coatomer Conformations and Interactions. Science. Epub: 10.1126/science.1221443
 


ii) Specificity and structural basis for protein-lipid interactions
within the bilayer

 
Functioning and processing of membrane proteins critically depend on the way their transmembrane domains (TMDs) are embedded in the membrane. Sphingolipids are structural components of membranes and can also act as intracellular second messengers. Not much is known of sphingolipids binding to TMDs of proteins within the hydrophobic bilayer, and how this could affect protein function. To our surprise, we found a direct and highly specific interaction of exclusively one sphingomyelin species, SM 18, with the TMD of the COPI machinery protein p24. Strikingly, the interaction depends on both the head group and the backbone of the sphingolipid, and on a signature (molecular recognition determining structure (MRDS) VXXTLXXIY within the TMD. Molecular dynamics simulations show a close interaction of SM 18 with the TMD (see figure on the left). We suggest a role of SM 18 in regulating the equilibrium between an inactive monomeric and an active oligomeric state of the p24 protein, which in turn regulates COPI-dependent transport. Bioinformatic analyses predict that the MRDS represents a conserved sphingolipid-binding cavity that exists in a variety of mammalian membrane proteins. Thus, in addition to a function as second messengers, sphingolipids can act as cofactors to regulate the function of transmembrane proteins. Our discovery of an unprecedented specificity of interaction of a TMD with an individual sphingolipid species adds to our understanding of why biological membranes are assembled from such a large variety of different lipids.
We have defined a number of trans-membrane proteins as candidates for specific interaction with sphingolipids, and in the future will investigate structure and function of such lipid/trans membrane complexes.

Collaborations with:  Gunnar von Heijne, Stockholm,
                               Erik Lindahl, Stockholm,
                               Patrick Elofsson, Stockholm,
                               Christoph Thiele, Bonn,
                               Rainer Pepperkok, EMBL, Heidelberg
                               Vivek Malhotra, Barcelona

 
Selected publications on Specificity and structural basis for protein-lipid interactions within the bilayer:

A. Karrenbauer, D. Jeckel. W. Just, R. Birk, R. R. Schmidt, J. E. Rothman, and F. Wieland (1991)  The Rate of Bulk Flow from the Golgi to the Plasma Membrane. Cell 63, 259-267.

D. Jeckel, A. Karrenbauer, K. N. J. Burger, G. van Meer, and F. Wieland (1992). Glucosylceramide is synthesized at the cytosolic surface of various Golgi subfractions. J. Cell Biol. 117, 259-267.

A. Brüning, A. Karrenbauer, E. Schnabel, and F. Wieland (1992) Brefeldin A-Induced Increase of Sphingomyelin Synthesis. J. Biol. Chem. 267, 5052-5055.

M. Murata, J. Peränen, R. Schreiner, F. Wieland, T. V. Kurzchalia, and K. Simons (1995) VIP21/caveolin is a cholesterol-binding protein. Proc. Natl. Acad. Sci. U.S.A. 92, 10339-10343.

H. Lannert, K. Gorgas, I. Meißner, F. Wieland, and D. Jeckel (1998) Lactosylceramide and subsequent glycosphingolipids are synthesized in the late Golgi. J. Biol. Chem. 273, 2939-2946.

B. Brügger, R. Sandhoff, S. Wegehingel, K. Gorgas, J. Malsam, B. Helms, W.-D. Lehmann, W. Nickel, and F. Wieland (2000) Evidence for Segregation of sphingomyelin and cholesterol during formation of COPI-coated vesicles. J. Cell Biol. 151, 507-517.

I. Gkantiragas, B. Brügger, E. Stüven, D. Kaloyanova, X. Li, K. Löhr, F. Lottspeich, F. T. Wieland, and B. Helms (2001) Sphingomyelin-enriched microdomains at the Golgi complex. Mol. Biol. Cell 12, 1819-1833.

P. Haberkant, O. Schmitt, F.-X. Contreras, C. Thiele, K. Hanada, H. Sprong, C. Reinhard, F. T. Wieland, B. Brügger (2008). Protein-sphingolipid interactions within cellular membranes. J. Lipid Res. 49(1):251-62.

F.X. Contreras, A.M. Ernst, F. Wieland and B. Brügger (2011). Specificity of intramembrane protein-lipid interactions. Cold Spring Harb Perspect Biol. Jun 1;3(6)

F.-X. Contreras, A.M. Ernst, P. Haberkant, P. Björkholm, E. Lindahl, B. Gönen, C. Tischer, A.   Elofsson, G. von Heijne, C. Thiele, R. Pepperkok, F. Wieland, and B. Brügger (2012) Molecular recognition of a single sphingolipid species by a protein’s transmembrane domain. Nature. 481:525-529.

A.M. Ernst, F.-X. Contreras, C. Thiele, F. Wieland & B. Brügger (2012). Mutual rocognition of sphingolipid molecular species in membranes. Biochim Biophys Acta - Biomemb. 1818(11): 2616-2622.
 

 

 
Download BZH-Report Wieland 2014-2016

Publications 


2015
Hacke M, Björkholm A, Hellwig P, Himmels P, Ruiz de Almodóvar C, Brügger B, Wieland F, and Ernst AM. Inhibition of Ebola virus glycoprotein-mediated cytotoxicity by targeting its transmembrane domain and cholesterol.
Nature Commun. 2015; July 9; &.7688. doi:10.1038/ncomms8688 PMID26158910.

Dodonova SO, Diestelkoetter-Bachert P, von Appen A, Hagen WJH, Beck R, Beck M, Wieland F, and Briggs JAG. A structure of the COPI coat and the role of coat proteins in membrane vesicle assembly.
Science. 349:195-198.

2014
Eckert ESP, Reckmann I, Hellwig A, Röhling S, Battari AE, Wieland FT, and Popoff V. Golgi phosphoprotein 3 trigers signal-mediated incorporation of glycosyltransferases into coatomer-coated (COPI) vesicles.
J Biol Chem. 2014; 289(45):31319-29.

Gerl MJ, Sachsenheimer T, Grzybek M, Coskun U, Wieland FT, and Brügger B. Analysis of transmembrane domains and lipid mdified peptides with matrix-assisted laser desorption ionization-time-of-flight mass spectrometry.
Anal Chem. 2014; 86(8):3722-26.

Björkholm P, Ernst AM, Hacke M, Wieland FT, and Brügger B. Identification of novel lipid-binding motifs in mammalian membrane proteins.
BiochimBiophys Acta Biomembranes. 2014; 1836:2066-70.

2013
Ernst AM, Brügger B. Sphingolipids as modulators of membrane proteins. Biochim Biophys Acta. 2013; Nov 5. doi:pii: S1388-1981(13)00239-4. 10.1016/ j.bbalip.2013.10.016. [Epub ahead of print]. Review.

Ozbalci C, Sachsenheimer T, Brügger B. Quantitative analysis of cellular lipids by nano-electrospray ionization mass spectrometry.
Methods Mol Biol. 2013; 1033:3-20. doi: 10.1007/978-1-62703-487-6_1.

Seehafer K, Rominger F, Helmchen G, Langhans M, Robinson DG, Ozata B, Brügger B Strating JR, van Kuppeveld FJ, Klein CD. Synthesis and Biological Properties of Novel Brefeldin A Analogues.
J Med Chem. 2013; Jul 8

Tan T, Ozbalci C, Brügger B, Rapaport D, Dimmer KS. Mcp1 and Mcp2, two novel proteins involved in mitochondrial lipid homeostasis.
J Cell Sci. 2013; Aug 15;126(Pt 16):3563-74

Adolf F, Herrmann A, Hellwig A, Beck R, Brügger B, Wieland FT. Scission of COPI and COPII vesicles is independent of GTP hydrolysis.
Traffic. 2013;14(8):922-32.

Ernst AM, Zacherl S, Herrmann A, Hacke M, Nickel W, Wieland FT, Brügger B. Differential transport of Influenza A neuraminidase signal anchor peptides to the plasma membrane.
FEBS Lett. 2013, 587(9):1411-7.

Haberkant P, Raijmakers R, Wildwater M, Sachsenheimer T, Brügger B, Maeda K, Houweling M, Gavin AC, Schultz C, van Meer G, Heck AJ, Holthuis JC. In vivo profiling and visualization of cellular protein-lipid interactions using bifunctional fatty acids.
Angew Chem Int Ed Engl. 2013; 52(14):4033-8.

Lorizate M, Sachsenheimer T, Glass B, Habermann A, Gerl MJ, Kräusslich HG, Brügger B. Comparative lipidomics analysis of HIV-1 particles and their producer cell membrane in different cell lines.
Cell Microbiol. 2013; 15(2):292-304.

2012
Krijnse Locker J, Chlanda P, Sachsenheimer T, Brügger B. Poxvirus membrane biogenesis: rupture not disruption. Cell Microbiol. 2012 Nov 21. doi: 10.1111/cmi.12072. [Epub ahead of print]

Duran JM, Campelo F, van Galen J, Sachsenheimer T, Sot J, Egorov MV, Rentero C, Enrich C, Polishchuk RS, Goñi FM, Brügger B, Wieland F, Malhotra V. Sphingomyelin organization is required for vesicle biogenesis at the Golgi complex. EMBO J. 2012 Nov 23;31(24):4535-46.

Krumpe K, Frumkin I, Herzig Y, Rimon N, Özbalci C, Brügger B, Rapaport D, Schuldiner M. Ergosterol content specifies targeting of tail-anchored proteins to mitochondrial outer membranes. Mol Biol Cell. 2012 Oct;23(20):3927-35.

Brügger B, Bankaitis VA. Lipids and vesicular transport. Biochim Biophys Acta. 2012 Aug;1821(8):1039.

Ernst AM, Contreras FX, Thiele C, Wieland F, Brügger B. Mutual recognition of sphingolipid molecular species in membranes. Biochim Biophys Acta - Biomemb. 2012 Jun 12;1818(11):2616-2622.

Brodde A, Teigler A, Brügger B, Lehmann WD, Wieland F, Berger J, Just WW. Impaired neurotransmission in ether lipid-deficient nerve terminals. Hum Mol Genet. 2012 Jun 15;21(12):2713-24.

Faini M, Prinz S, Beck R, Schorb M, Riches JD, Bacia K, Brügger B, Wieland FT, Briggs JA. The Structures of COPI-Coated Vesicles Reveal Alternate Coatomer Conformations and Interactions. Science. 2012 Jun 15;336(6087):1451-4.

Zhao H, Williams DE, Shin JB, Brügger B, Gillespie PG. Large membrane domains in hair bundles specify spatially constricted radixin activation. J Neurosci. 2012 Mar 28;32(13):4600-9.

Pevzner I, Strating J, Lifshitz L, Parnis A, Glaser F, Herrmann A, Brügger B, Wieland F, Cassel D. Distinct role of subcomplexes of the COPI coat in the regulation of ArfGAP2 activity. Traffic. 2012 Feb 29. doi: 10.1111/j.1600-0854.2012.01349.x.

Contreras, FX, Ernst, AM, Haberkant, P, Björkholm, P, Lindahl, E, Gönen, B, Tischer, C, Elofsson, A, von Heijne, G, Thiele, C, Pepperkok, R, Wieland, F, Brügger, B. Molecular recognition of a single sphingolipid species by a protein's transmembrane domain. Nature 2012 Jan 9. doi: 10.1038/nature 10742.

Haag, M, Schmidt, A, Sachsenheimer, T, Brügger, B. Quantification of Signaling Lipids by Nano-Electrospray Ionization Tandem Mass Spectrometry (Nano-ESI MS/MS). Metabolites 2012, 2(1), 57-76; doi:10.3390/metabo 2010057

2011
Yurlova L, Kahya N, Aggarwal S, Kaiser HJ, Chiantia S, Bakhti M, Pewzner-Jung Y, Ben-David O, Futerman AH, Brügger B, Simons M. Self-segregation of myelin membrane lipids in model membranes. Biophys J. 2011 Dec 7;101(11):2713-20.

Schmidt, A, Oberle, N, Weiß, EM, Vobis, D, Frischbutter, S, Baumgrass, R, Falk, CS, Haag, M, Brügger, B, Lin, H, Mayr, GW, Reichardt, P, Gunzer, M, Suri-Payer E, Krammer PH. Human regulatory T cells rapidly suppress T Cell Receptor-induced calcium signals, NF-κB and NFAT activation in conventional CD4+CD25- T cells. Sci Signal. 20 December 2011: ra90
DOI: 10.1126/scisignal.2002179.

Sancar, G, Sancar, C, Brügger, B, Ha, N, Sachsenheimer, T, Gin, E, Wdowik, S, Lohmann, I, Wieland, F, Hoefer, T, Diernfellner, AC, Brunner, M. A global circadian repressor controls anti-phasic expression of metabolic genes in Neurospora. Mol Cell 2011 Dec 9;44(5):687-97.

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. Phenotypic profiling of the human genome reveals gene products involved in plasma membrane targeting of SRC kinases. Genome Res. 2011 Nov;21(11):1955-68.

Popoff V, Adolf F, Brügger B, Wieland F. COPI Budding within the Golgi Stack. Cold Spring Harb Perspect Biol. 2011 Nov 1;3(11).

Popoff V, Langer JD, Reckmann I, Hellwig A, Kahn RA, Brügger B, Wieland FT. Several ADP-ribosylation factor (Arf) isoforms support COPI vesicle formation. J Biol Chem. 2011 Oct 14;286(41):35634-42.

Beck R, Prinz S, Diestelkötter-Bachert P, Röhling S, Adolf F, Hoehner K, Welsch S, Ronchi P, Brügger B, Briggs JA, Wieland F. Coatomer and dimeric ADP ribosylation factor 1 promote distinct steps in membrane scission. J Cell Biol. 2011 Sep 5;194(5):765-77.

Ben-David O, Pewzner-Jung Y, Brenner O, Laviad EL, Kogot-Levin A, Weissberg I, Biton IE, Pienik R, Wang E, Kelly S, Alroy J, Raas-Rothschild A, Friedman A, Brügger B, Merrill AH Jr, Futerman AH. Encephalopathy caused by ablation of very long acyl chain ceramide synthesis may be largely due to reduced galactosylceramide levels. J Biol Chem. 2011 Aug 26;286(34):30022-33.

Habermehl D, Parkitna JR, Kaden S, Brügger B, Wieland F, Gröne HJ, Schütz G. Glucocorticoid Activity during Lung Maturation Is Essential in Mesenchymal and Less in Alveolar Epithelial Cells. Mol Endocrinol. 2011 Aug;25(8):1280-8.

Kou J, Kovacs GG, Höftberger R, Kulik W, Brodde A, Forss-Petter S, Hönigschnabl S, Gleiss A, Brügger B, Wanders R, Just W, Budka H, Jungwirth S, Fischer P, Berger J. Peroxisomal alterations in Alzheimer's disease. Acta Neuropathol. 2011 Sep;122(3):271-83.

Kupke T, Di Cecco L, Müller HM, Neuner A, Adolf F, Wieland F, Nickel W, Schiebel E. Targeting of Nbp1 to the inner nuclear membrane is essential for spindle pole body duplication. EMBO J. 2011 Jul 22;30(16):3337-52.

Shtutman M, Baig M, Levina E, Hurteau G, Lim CU, Broude E, Nikiforov M, Harkins TT, Carmack CS, Ding Y, Wieland F, Buttyan R, Roninson IB. Tumor-specific silencing of COPZ2 gene encoding coatomer protein complex subunit ζ 2 renders tumor cells dependent on its paralogous gene COPZ1. Proc Natl Acad Sci U S A. 2011 Jul 26;108(30):12449-54.

Sahlmüller MC, Strating JR, Beck R, Eckert P, Popoff V, Haag M, Hellwig A, Berger I, Brügger B, Wieland FT. Recombinant heptameric coatomer complexes: novel tools to study isoform-specific functions. Traffic 2011 Jun;12(6):682-92

Contreras FX, Ernst AM, Wieland F, Brügger B. Specificity of intramembrane protein-lipid interactions. Cold Spring Harb Perspect Biol. 2011 Jun 1;3(6). pii: a004705. Review

Beck R, Brügger B, Wieland F. GAPs in the context of COPI: Enzymes, coat components or both? Cell Logist. 2011 Mar;1(2):52-54.

Welti S, Kühn S, D'Angelo I, Brügger B, Kaufmann D, Scheffzek K. Structural and biochemical consequences of NF1 associated nontruncating mutations in the Sec14-PH module of neurofibromin. Hum Mutat. 2011 Feb;32(2):191-7.

Merz A, Long G, Hiet MS, Brügger B, Chlanda P, Andre P, Wieland F, Krijnse-Locker J, Bartenschlager R Biochemical and morphological properties of hepatitis C virus particles and determination of their lipidome. J Biol Chem. 2011 Jan 28;286(4):3018-32.

2010
Erez E, Stjepanovic G, Zelazny AM, Brügger B, Sinning I, Bibi E. Genetic evidence for functional interaction of the Escherichia coli signal recognition particle receptor with acidic lipids in vivo.
J Biol Chem. 2010; 285(52):40508-14.

Beck R, Brügger B, Wieland FT. Membrane deformation and separation.
F1000 Biol Rep. 2010; 2. pii: 35.

Osman C, Haag M, Wieland FT, Brügger B, Langer T. A mitochondrial phosphatase required for cardiolipin biosynthesis: the PGP phosphatase Gep4.
EMBO J. 2010; 29(12):1976-87.

Lavieu G, Orci L, Shi L, Geiling M, Ravazzola M, Wieland F, Cosson P, Rothman JE. Induction of cortical endoplasmic reticulum by dimerization of a coatomer-binding peptide anchored to endoplasmic reticulum membranes.
Proc Natl Acad Sci U S A. 2010;107(15):6876-81.

Pewzner-Jung Y, Park H, Laviad EL, Silva LC, Lahiri S, Stiban J, Erez-Roman R, Brügger B, Sachsenheimer T, Wieland F, Prieto M, Merrill AH Jr, Futerman AH.
A critical role for ceramide synthase 2 in liver homeostasis: I. alterations in lipid metabolic pathways.
J Biol Chem. 2010; 285(14):10902-10.

Ernst AM, Contreras FX, Brügger B, Wieland F. Determinants of specificity at the protein-lipid interface in membranes.
FEBS Lett. 2010; 584(9):1713-20. Review.

Mora R, Dokic I, Kees T, Hüber CM, Keitel D, Geibig R, Brügger B, Zentgraf H, Brady NR, Régnier-Vigouroux A. Sphingolipid rheostat alterations related to transformation can be exploited for specific induction of lysosomal cell death in murine and human glioma.
Glia. 2010; 58(11):1364-83.

2009
Emr S, Glick BS, Linstedt AD, Lippincott-Schwartz J, Luini A, Malhotra V, Marsh BJ, Nakano A, Pfeffer SR, Rabouille C, Rothman JE, Warren G, Wieland FT. Journeys through the Golgi--taking stock in a new era.
J Cell Biol. 2009; 187(4):449-53. Review.

Beck R, Rawet M, Wieland FT, Cassel D. The COPI system: molecular mechanisms and function.
FEBS Lett. 2009; 583(17):2701-9. Review.
Erratum in:
FEBS Lett. 2009; 583(21):3541.

Lorizate M, Brügger B, Akiyama H, Glass B, Müller B, Anderluh G, Wieland FT, Kräusslich HG. Probing HIV-1 membrane liquid order by Laurdan staining reveals producer cell-dependent differences.
J Biol Chem. 2009; 284(33):22238-47.

Rutz C, Satoh A, Ronchi P, Brügger B, Warren G, Wieland FT. Following the fate in vivo of COPI vesicles generated in vitro.
Traffic. 2009; 10(8):994-1005.

Osman C, Haag M, Potting C, Rodenfels J, Dip PV, Wieland FT, Brügger B, Westermann B, Langer T. The genetic interactome of prohibitins: coordinated control of cardiolipin and phosphatidylethanolamine by conserved regulators in mitochondria.
J Cell Biol. 2009; 184(4):583-96.

Beck R, Adolf F, Weimer C, Bruegger B, Wieland FT. ArfGAP1 activity and COPI vesicle biogenesis.
Traffic. 2009; 10(3):307-15.

Saher G, Quintes S, Möbius W, Wehr MC, Krämer-Albers EM, Brügger B, Nave KA. Cholesterol regulates the endoplasmic reticulum exit of the major membrane protein P0 required for peripheral myelin compaction.
J Neurosci. 2009; 29(19):6094-104.

2008
Langer JD, Roth CM, Béthune J, Stoops EH, Brügger B, Herten DP, Wieland FT.
A conformational change in the alpha-subunit of coatomer induced by ligand binding to gamma-COP revealed by single-pair FRET.
Traffic. 2008. 9(4):597-607.

Kwa LG, Wegmann D, Brügger B, Wieland FT, Wanner G, Braun P. Mutation of a single residue, beta-glutamate-20, alters protein-lipid interactions of light harvesting complex II.
Mol Microbiol. 2008; 67(1):63-77.

Haberkant P, Schmitt O, Contreras FX, Thiele C, Hanada K, Sprong H, Reinhard C, Wieland FT, Brügger B. Protein-sphingolipid interactions within cellular membranes. J Lipid Res. 2008; 49(1):251-62.

Trajkovic K, Hsu C, Chiantia S, Rajendran L, Wenzel D, Wieland F, Schwille P, Brügger B, Simons M. Ceramide triggers budding of exosome vesicles into multivesicular endosomes.
Science. 2008; 319(5867):1244-7.

Beck R, Sun Z, Adolf F, Rutz C, Bassler J, Wild K, Sinning I, Hurt E, Brügger B, Béthune J, Wieland F. Membrane curvature induced by Arf1-GTP is essential for vesicle formation.
Proc Natl Acad Sci U S A. 2008; 105(33):11731-6.

Superti-Furga G, Wieland F, Cesareni G. Finally: The digital, democratic age of scientific abstracts.
FEBS Lett. 2008; 582(8):1169.

Zitzler S, Hellwig A, Hartl FU, Wieland F, Diestelkötter-Bachert P. Distinct binding sites for the ATPase and substrate-binding domain of human Hsp70 on the cell surface of antigen presenting cells.
Mol Immunol. 2008; 45(15):3974-83.

Krauss M, Jia JY, Roux A, Beck R, Wieland FT, De Camilli P, Haucke V.
Arf1-GTP-induced tubule formation suggests a function of Arf family proteins in curvature acquisition at sites of vesicle budding.
J Biol Chem. 2008; 283(41):27717-23.

Weimer C, Beck R, Eckert P, Reckmann I, Moelleken J, Brügger B, Wieland F. Differential roles of ArfGAP1, ArfGAP2, and ArfGAP3 in COPI trafficking.
J Cell Biol. 2008; 183(4):725-35.

2007
Kassmann CM, Lappe-Siefke C, Baes M, Brügger B, Mildner A, Werner HB, Natt O, Michaelis T, Prinz M, Frahm J, Nave KA. Axonal loss and neuroinflammation caused by peroxisome-deficient oligodendrocytes.
Nat Genet. 2007, 39(8):969-76.

Brügger B, Krautkrämer E, Tibroni N, Munte CE, Rauch S, Leibrecht I, Glass B, Breuer S, Geyer M, Kräusslich HG, Kalbitzer HR, Wieland FT, Fackler OT. Human immunodeficiency virus type 1 Nef protein modulates the lipid composition of virions and host cell membrane microdomains.
Retrovirology. 2007, 4:70

Findeisen F, Linder JU, Schultz A, Schultz JE, Brügger B, Wieland F, Sinning I, Tews I. The structure of the regulatory domain of the adenylyl cyclase Rv1264 from Mycobacterium tuberculosis with bound oleic acid.
J. Mol. Biol. 2007, 369: 1282-1295.

Sun Z, Anderl F, Fröhlich K, Zhao L, Hanke S, Brügger B, Wieland F, Béthune J. Multiple and stepwise interactions between coatomer and ADP-ribosylation factor-1 (Arf1)-GTP.
Traffic 2007, 8: 582-593.

Langer JD, Stoops EH, Béthune J, Wieland FT. Conformational changes of coat proteins during vesicle formation.
FEBS Lett. 2007, 581: 2083-2088.

Vetrivel KS, Gong P, Bowen JW, Cheng H, Chen Y, Carter M, Nguyen PD, Placanica L, Wieland FT, Li YM, Kounnas MZ, Thinakaran G. Dual roles of the transmembrane protein p23/TMP21 in the modulation of amyloid precursor protein metabolism.
Mol. Neurodegener. 2007, 8, 2:4.

Li X, Kaloyanova D, van Eijk M, Eerland R, van der Goot G, Oorschot V, Klumperman J, Lottspeich F, Starkuviene V, Wieland FT, Helms JB. Involvement of a Golgi-resident GPI-anchored Protein in Maintenance of the Golgi Structure.
Mol. Biol. Cell 2007, 18:1261-1271.

Moelleken J, Malsam J, Betts MJ, Movafeghi A, Reckmann I, Meissner I, Hellwig A, Russell RB, Söllner T, Brügger B, Wieland FT. Differential localization of coatomer complexes isoforms within the Golgi apparatus.
Proc. Natl. Acad. Sci. USA 2007, 104: 4425-4430.

2006
S. Takamori, M. Holt, K. Stenius, E.A. Lemke, M. Grønborg, D. Riedel, H. Urlaub, S. Schenck, B. Brügger, P. Ringler, S.A. Müller, B. Rammner, F. Gräter, J.S. Hub, B.L. De Groot, G. Mieskes, Y. Moriyama, J. Klingauf, H. Grubmüller, J. Heuser, F. Wieland, and R. Jahn (2006): Molecular Anatomy of a Trafficking Organelle. Cell 127:831-846.

J. Béthune, M. Kol, J. Hoffmann, I. Reckmann, B. Brügger, F. Wieland (2006): Coatomer, the coat protein of COPI transport vesicles, discriminates endoplasmic reticulum residents from p24 proteins. Mol. Cell. Biol. 26:8011-8021.

J. Béthune, F. Wieland, J. Moelleken (2006): COPI-mediated transport. J. Membr. Biol. 211:65-79.

B. Brügger, B. Glass, P. Haberkant, I. Leibrecht, F.T. Wieland and H.-G. Kräusslich. 2006. The HIV lipidome: A raft with an unusual composition. Proc. Natl. Acad. Sci. USA 103:2641-2646. (10.452)

2005
G. Saher, B. Brügger, C. Lappe-Siefke, W. Möbius, R. Tozawa, M. C. Wehr, F. Wieland, S. Ishibashi, and K.-A. Nave (2005): High level cholesterol is essential for myelin membrane growth. Nature Neurosci. 8:468-475.

2004
R. Schneiter, B. Brügger, C. M. Amann, G. D. Prestwich, R. F. Epand, G. Zellnig, F. T. Wieland, and R. M. Epand. (2004) Identification and biophysical characterization of a very-long-chain-fatty-acid-substituted phosphatidylinositol in yeast subcellular membranes. Biochem. J. 381:941-949.

M. G. Theis, A. Knorre, B. Kellersch, J. Moelleken, F. T. Wieland, W. Kolanus, and M. Famulok. (2004) Discriminatory aptamer reveals serum response element transcription regulated by cytohesin-2. Proc. Natl. Acad. Sci. U.S.A. 101:11221-11226.

B. Brügger, C. Graham, I. Leibrecht, E. Mombelli, A. Jen, F. Wieland, and R. Morris. (2004) The membrane domains occupied by glycosylphosphatidylinositol-anchored prion protein and Thy-1 differ in lipid composition. J. Biol. Chem. 279:7530-7536.

B. Brügger and F. T. Wieland (2004). Mechanismen der COPI-Vesikelbiogenese. Biospektrum I, 30-33 (Review).

D. Wegmann, P. Hess, C. Baier, F. T. Wieland and C. Reinhard (2004). Novel isotypic g/z-subunits reveal three coatomer complexes in mammals. Mol. Cell. Biol. 3, 1070-1080. Supplemental Materials [PDF]


Selected publications:

2003
S. Neumann, E. Petfalski, B. Brügger, H. Großhans, F. T. Wieland, D. Tollervey and E. Hurt (2003). Formation and nuclear export of tRNA, rRNA and mRNA is regulated by the ubiquitin ligase Rsp5p. EMBO Rep. 12:1156-1162.

C. Rodemer, T.P. Thai, B, Brügger, T. Kaercher, H. Werner, K.A, Nave, F. Wieland, K. Gorgas, W.W. Just (2003) Inactivation of ether lipid biosynthesis causes male infertily, defects in eye development and optic nerve hypoplasia in mice. Hum. Mol. Genet. 12:1881-1895.

C. Eroglu, B. Brügger, F. T. Wieland, I. Sinning (2003) Glutamate-binding affinity of Drosophila metabotropic glutamate receptor is modulated by association with lipid rafts. Proc Natl Acad Sci U S A. 100(18):10219-24.

C. Reinhard, M. Schweikert, F. T. Wieland, W. Nickel (2003) Functional reconstitution of COPI coat assembly and disassembly using chemically defined components. Proc Natl Acad Sci U S A: 100(14):8253-7.

A. Kruljac-Letunic, J. Moelleken, A. Kallin, F. T. Wieland, A. Blaukat (2003) The tyrosine kinase Pyk2 regulates Arf1 activity by phosphorylation and inhibition of the Arf-GTPase-activating protein ASAP1. J Biol Chem. 278(32):29560-70.

2002
T. Becker, F. U. Hartl, F. T. Wieland (2002) CD40, an extracellular receptor for binding and uptake of Hsp70-peptide complexes. J Cell Biol. 158(7):1277-85.

N. Jenne, K. Frey, B. Brügger, F. T. Wieland (2002) Oligomeric state and stoichiometry of p24 proteins in the early secretory pathway. J Biol Chem. 277(48):46504-11

2001
D. U. Gommel, A. R. Memon, A. Heiss, F. Lottspeich, J. Pfannstiel, J. Lechner, C. Reinhard, J. B. Helms, W. Nickel, F. T. Wieland (2001) Recruitment to Golgi Membranes of ADP-Ribosylation Factor is mediated by the cytoplasmic domain of p23, EMBO J. 20, 6751-6760.

I. Gkantiragas, B. Brügger, E. Stüven, D. Kaloyanova, X. Li, K. Löhr, F. Lottspeich, F. T. Wieland, and B. Helms (2001) Sphingomyelin-enriched microdomains at the Golgi complex. Mol. Biol. Cell 12, 1819-1833.

2000
B. Brügger, R. Sandhoff, S. Wegehingel, K. Gorgas, J. Malsam, B. Helms, W.-D. Lehmann, W. Nickel, and F. Wieland (2000) Evidence for Segregation of sphingomyelin and cholesterol during formation of COPI-coated vesicles. J. Cell Biol. 151, 507-517.

1999
J. Malsam, D. Gommel, F. T. Wieland, and W. Nickel (1999) A role for ADP-ribosylation factor in the control of cargo uptake during COPI-vesicle biogenesis. FEBS Lett. 462, 267-272.

R. Schneiter, B. Brügger, G. Zellnig, A. Leber, S. Eder, M. Lampl, K. Athenstaedt, C. Hrastnik, R. Sandhoff, G. Daum, F. Paltauf, F. T. Wieland, and S. Kohlwein (1999) ESI-MS/MS analysis of the lipid molecular species composition of yeast subcellular membranes reveals acyl chain-based sorting/remodeling of distinct molecular species at the plasma membrane. J. Cell Biol. 146,741-54.

*Wieland and C. Harter (1999) Mechanisms of vesicle formation: insights form the COP system. Curr. Opin. Cell Biol. 11, 440-446.

M.-D. Ledesma, B. Brügger, C. Bünning, F.T. Wieland, and C. G. Dotti (1999) Maturation of the axonal plasma membrane requires upregulations of sphingomyelin synthesis and formation of protein-lipid complexes. EMBO J. 18, 1761-1771.

L. Zhao, B. Helms, J. Brunner, and F. Wieland (1999) GTP-dependent Binding of ARF to Coatomer in Close Proximity to the Binding Site for Dilysine Retrieval Motifs and p23. J. Biol. Chem. 274, 14198-14203.

M. Bremser, W. Nickel, M. Schweikert, M. Ravazzola, M. Amherd, C.A. Hughes, T.H. Söllner, J. E. Rothman, and F. T. Wieland (1999) Coupling of coat assembly and vesicle budding to packaging of putative cargo receptors. Cell 96, 495-506.

C. Reinhard, C. Harter, M. Bremser, B. Brügger, K. Sohn. B. Helms, and F. Wieland (1999) Receptor induced polymerisation of coatomer. Proc. Natl. Acad. Sci U.S.A. 96, 1224-1228.

1998
C. Harter, and F. Wieland (1998) A single binding site for di-lysine motifs and p23 within the g-subunit of coatomer. Proc. Natl. Acad. Sci. USA. 95,11649-11654

W. Nickel, J. Malsam, K. Gorgas, M. Ravazzola, N. Jenne, J. B. Helms, and F. T. Wieland (1998) Uptake by COPI-coated vesicles of both anterograde and retrograde cargo is inhibited by GTP-g-S in vitro. J. Cell Sci. 111, 3081-3090

J. Pavel, C. Harter, and F. Wieland (1998) Reversible dissociation of coatomer: Functional characterization of a b/d-coat protein subcomplex. Proc. Natl. Acad. Sci. U.S.A., 95, 2140-2145.

1997
W. Nickel, K. Sohn, C. Bünning, and F. 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.

B. Brügger, G. Erben, R. Sandhoff, F. T. Wieland, and W. D. Lehmann. (1997) Quantitative analysis of biological membrane lipids at the low picomole level by nano-electrospray ionization tandem mass spectrometry. Proc. Natl. Acad. Sci. U.S.A. 94, 2339-2344


L. Zhao, B. Helms, B. Brügger, C. Harter, B. Martoglio, R. Graf, J. Brunner, and F. T. Wieland (1997) Direct and GTP-dependent interaction of ADP-ribosylation factor I with coatomer subunit b. Proc. Natl. Acad. Sci. U.S.A. 94, 4418-4423.

1996
K. Sohn, L. Orci, M. Ravazzola, M. Amherdt, M. Bremser, F. Lottspeich, K. Fiedler, J. B. Helms, and F. Wieland (1996) A major transmembrane protein of Golgi-derived COPI-coated vesicles involved in coatomer binding. J. Cell Biol. 135, 1238-1248

D. Faulstich, S. Auerbach, L. Orci, M. Ravazzola, S. Wegehingel, F. Lottspeich, G. Stenbeck, C. Harter, F. T. Wieland, and H. Tschochner (1996) Architecture of coatomer: molecular characterization of d-COP and protein interactions within the complex. J. Cell Biol. 135, 53-61.

*J. E. Rothman and F. T. Wieland (1996) Protein sorting by transport vesicles. Science 272, 227-234.

C. Harter, J. Pavel, F. Coccia, E. Draken, S. Wegehingel, H. Tschochner, and F. Wieland (1996) Non-clathrin-coat protein g, a subunit of coatomer, binds to the cytoplasmic dilysine motif of membrane proteins of the early secretory pathway. Proc. Natl. Acad. Sci. U.S.A. 93, 1902-1906

1995B. Gerich, L. Orci, H. Tschochner, F. Lottspeich, M. Ravazzola, M. Amherdt, F. Wieland, and C. Harter (1995) Non-clathrin-coat protein a is a conserved subunit of coatomer and in Saccharomyces cerevisiae is essential for growth. Proc. Natl. Acad. Sci. U.S.A. 92, 3229-3233.

M. Murata, J. Peränen, R. Schreiner, F. Wieland, T. V. Kurzchalia, and K. Simons (1995) VIP21/caveolin is a cholesterol-binding protein. Proc. Natl. Acad. Sci. U.S.A. 92, 10339-10343

1993
G. Stenbeck, C. Harter, A. Brecht, D. Herrmann, F. Lottspeich, L. Orci, and F. T. Wieland (1993) b'-COP, a Novel Subunit of Coatomer. EMBO J. 12, 2841-2845

1992
D. Jeckel, A. Karrenbauer, K. N. J. Burger, G. van Meer, and F. Wieland (1992) Glucosylceramide is synthesized at the cytosolic surface of various Golgi subfractions. J. Cell Biol. 117, 259-267

1991
T. Serafini, G. Stenbeck, A. Brecht, F. Lottspeich, L. Orci, J. E. Rothman, and F. Wieland (1991) A Coat Subunit of Golgi-Derived non-Clathrin Coated Vesicles with Homology to the Clathrin Coated Vesicle Coat Protein b-Adaptin. Nature 349, 215-220.

1990
A. Karrenbauer, D. Jeckel. W. Just, R. Birk, R. R. Schmidt, J. E. Rothman, and F. Wieland (1990) The Rate of Bulk Flow from the Golgi to the Plasma Membrane. Cell 63, 259-267.

1988
M. R. Block, B. S. Glick, C. A. Wilcox, F. Wieland, and J. Rothman (1988) Purification of an N-Ethylmaleimide-Sensitive Protein Catalyzing Vesicular Transport. Proc. Natl. Acad. Sci.U.S.A. 85, 7852-7856.

1987
F. Wieland, M. Gleason, T. Serafini, J. Rothman (1987) The Rate of Bulk Flow from the Endoplasmic Reticulum to the Cell Surface. Cell 50, 289-300.

1986
G. Paul, F. Lottspeich, and F. Wieland (1986) Asparaginyl-N-Acetylgalactosamine: Linkage Unit of Halobacterial Glycosaminoglycan. J. Biol. Chem. 261, 1020-1024.

1983
F. Wieland, R. Heitzer, and W. Schäfer (1983) Asparaginyl-Glucose: Novel Type of Carbohydrate Linkage. Proc. Natl. Acad. Sci. U.S.A 80, 5470-5474

1978
F. Wieland, E. A. Siess, L. Renner, C. Verfürth, and F. Lynen (1978) Distribution of Yeast Fatty Acid Synthetase subunits: Threedimensional Model of the Enzyme. Proc. Natl. Acad. Sci. U.S.A. 75, 5792-5796.

CV 


                     CURRICULUM VITAE
 
Education:   Study of Chemistry at the University of Munich
                    Master's Degree in chemistry                                                      1975

                    PhD at the Max-Planck-Institute for Biochemistry
                    in Martinsried/Munich with Feodor Lynen                                      1975 - 1978

Career:        Wissenschaftlicher Assistent (time-limited position for research)
                    at the Max-Planck-Institute                                                         1976 - 1978

                    Akademischer Rat at the University of Regensburg                        1978 - 1984

                    Member of SFB 43 (Collaborative Research Program), Regensburg 1981 - 1988
                    "Biochemistry of membranes and cell surfaces".

                    Habilitation for Biochemistry, venia legendi                                  1984

                     Akademischer Oberrat at the University of Regensburg                1984 - 1986

                     Research award by the Deutsche Forschungsgemeinschaft           1986 - 1988
                     (Dept. of Biochemistry, Stanford University, CA., USA)

                     Full professor and director of the Institute for Biochemistry I  
                     at the University of Heidelberg                                                   1988 - 1997

                     Chairman of SFB 352 (collaborative research program)                1991 - 2003
                     Heidelberg: "Molecular mechanisms of intracellular
                     transport processes"

                     Dean of the faculty “Naturwissenschaftliche Medizin”                   1991 - 1992

                     Member for Biochemistry of the search committee
                     “Preclinical Medicine” at the Charité, Humboldt University Berlin   1991 - 1992

                     President elect of the German Society for Biochemistry and
                     Molecular Biology (GBM)                                                           2003 - 2005

                     President GBM   2005 - 2007

                     Founding Director of the Heidelberg Biochemistry-Centre (BZH)   1997 - 2003

                     Managing Editor FEBS Letters   2001 - present

                     Chairman of SFB 638 (collaborative research program)               2003 - present
                     Heidelberg: ”Dynamics of macromolecular complexes
                     in biosynthetic transport”

Awards:        Research award from the German Research Council                   1986 - 1988

                     Honorary member of the Charité, Humboldt University Berlin      1993

                     Elected member of EMBO                                                         2000

                     Heinrich Wieland Prize                                                             2001

                     Elected Member of the Deutsche Akademie der Naturforscher     2003
                     Leopoldina (German National Academy of Sciences)

                     Feldberg Foundation Prize                                                        2006

                     Elected Member of the Academia Europea                                  2011

Lab Members 



 
Elena Porcellato
PhD student

Lab:Room 326 / Phone: +49 6221 54-5420
Mail:elena.porcellato@bzh.uni-heidelberg.de

 RoomPhone
LAB 326 +49 6221 54-5420
E-Mail elena.porcellato@bzh.uni-heidelberg.de
Ingeborg Reckmann
TA

Lab:Room 326 / Phone: +49 6221 54-5420
Mail:inge.reckmann@bzh.uni-heidelberg.de

 RoomPhone
LAB 326 +49 6221 54-5420
E-Mail inge.reckmann@bzh.uni-heidelberg.de
Barbara Schröter
secretary

Office:Room 309 / Phone: +49 6221 54-4160
Mail:barbara.schroeter@bzh.uni-heidelberg.de

 RoomPhone
OFFICE 309 +49 6221 54-4160
E-Mail barbara.schroeter@bzh.uni-heidelberg.de
Xiyan Zhao
PhD student

Lab:Room 327 / Phone: +49 6221 54-4688
Mail:xiyan.zhao@bzh.uni-heidelberg.de

 RoomPhone
LAB 327 +49 6221 54-4688
E-Mail xiyan.zhao@bzh.uni-heidelberg.de

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Secretary: Barbara Schröter
Office:
+49 6221 54-4160
Fax:
+49 6221 54-4366
E-Mail:
barbara.schroeter@bzh.uni-heidelberg.de

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