Endosome and Golgi-associated degradation (EGAD) of membrane proteins regulates sphingolipid metabolism
DC Element | Wert | Sprache |
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dc.contributor.author | Schmidt, Oliver | |
dc.contributor.author | Weyer, Yannick | |
dc.contributor.author | Baumann, Verena | |
dc.contributor.author | Widerin, Michael A. | |
dc.contributor.author | Eising, Sebastian | |
dc.contributor.author | Angelova, Mihaela | |
dc.contributor.author | Schleiffer, Alexander | |
dc.contributor.author | Kremser, Leopold | |
dc.contributor.author | Lindner, Herbert | |
dc.contributor.author | Peter, Matthias | |
dc.contributor.author | Froehlich, Florian | |
dc.contributor.author | Teis, David | |
dc.date.accessioned | 2021-12-23T16:23:50Z | - |
dc.date.available | 2021-12-23T16:23:50Z | - |
dc.date.issued | 2019 | |
dc.identifier.issn | 02614189 | |
dc.identifier.uri | https://osnascholar.ub.uni-osnabrueck.de/handle/unios/14681 | - |
dc.description.abstract | Cellular homeostasis requires the ubiquitin-dependent degradation of membrane proteins. This was assumed to be mediated exclusively either by endoplasmic reticulum-associated degradation (ERAD) or by endosomal sorting complexes required for transport (ESCRT)-dependent lysosomal degradation. We identified in Saccharomyces cerevisiae an additional pathway that selectively extracts membrane proteins at Golgi and endosomes for degradation by cytosolic proteasomes. One endogenous substrate of this endosome and Golgi-associated degradation pathway (EGAD) is the ER-resident membrane protein Orm2, a negative regulator of sphingolipid biosynthesis. Orm2 degradation is initiated by phosphorylation, which triggers its ER export. Once on Golgi and endosomes, Orm2 is poly-ubiquitinated by the membrane-embedded ``Defective in SREBP cleavage'' (Dsc) ubiquitin ligase complex. Cdc48/VCP then extracts ubiquitinated Orm2 from membranes, which is tightly coupled to the proteasomal degradation of Orm2. Thereby, EGAD prevents the accumulation of Orm2 at the ER and in post-ER compartments and promotes the controlled de-repression of sphingolipid biosynthesis. Thus, the selective degradation of membrane proteins by EGAD contributes to proteostasis and lipid homeostasis in eukaryotic cells. | |
dc.description.sponsorship | Austrian Science FundAustrian Science Fund (FWF) [FWF-Y444-B12, P30263, P29583]; MCBO [W1101-B18]; EMBO/Marie Curie [ALTF 642-2012]; EMBO/Marie Curie (EMBOCOFUND2010) [GA-2010-267146]; MUI-START [2013042023]; Tiroler Wissenschaftsfond; DFGGerman Research Foundation (DFG)European Commission [FR 3647/2-1, SFB 944]; European Research Council (ERC)European Research Council (ERC)European Commission; Swiss National Science Foundation (SNSF)Swiss National Science Foundation (SNSF); ETH ZurichETH Zurich; We would like to thank Theresa Dunn, Peter Espenshade, Kai-Uwe Frohlich, Ben Glick, Robbie Loewith, Ming Li, Carl Mann, Howard Riezman, Chris Stephan, and Jonathan Weissman for providing reagents. Work in the Teis laboratory was supported by the Austrian Science Fund (FWF-Y444-B12, P30263, P29583) and MCBO (W1101-B18) to D.T and EMBO/Marie Curie (ALTF 642-2012; EMBOCOFUND2010, GA-2010-267146), MUI-START (2013042023), and ``Tiroler Wissenschaftsfond'' to O.S. Work in the Frohlich laboratory is supported by a DFG grant FR 3647/2-1 and the SFB 944. Work in the Peter laboratory was supported by funding from the European Research Council (ERC), the Swiss National Science Foundation (SNSF), and ETH Zurich. | |
dc.language.iso | en | |
dc.publisher | WILEY | |
dc.relation.ispartof | EMBO JOURNAL | |
dc.subject | Biochemistry & Molecular Biology | |
dc.subject | Cell Biology | |
dc.subject | endosomes | |
dc.subject | ER | |
dc.subject | GLOBAL ANALYSIS | |
dc.subject | Golgi | |
dc.subject | KINASE YPK1 | |
dc.subject | MULTIVESICULAR BODIES | |
dc.subject | proteasome | |
dc.subject | QUALITY-CONTROL | |
dc.subject | RECRUITS CDC48 | |
dc.subject | RETICULUM-ASSOCIATED DEGRADATION | |
dc.subject | SACCHAROMYCES-CEREVISIAE | |
dc.subject | sphingolipids | |
dc.subject | SREBP CLEAVAGE | |
dc.subject | ubiquitin | |
dc.subject | UBIQUITIN-LIGASE | |
dc.title | Endosome and Golgi-associated degradation (EGAD) of membrane proteins regulates sphingolipid metabolism | |
dc.type | journal article | |
dc.identifier.doi | 10.15252/embj.2018101433 | |
dc.identifier.isi | ISI:000478078000006 | |
dc.description.volume | 38 | |
dc.description.issue | 15 | |
dc.contributor.orcid | 0000-0002-8181-0253 | |
dc.contributor.orcid | 0000-0002-2612-6774 | |
dc.contributor.orcid | 0000-0001-6251-2747 | |
dc.contributor.orcid | 0000-0002-0495-9695 | |
dc.contributor.orcid | 0000-0002-7921-4663 | |
dc.contributor.orcid | 0000-0001-8307-2189 | |
dc.identifier.eissn | 14602075 | |
dc.publisher.place | 111 RIVER ST, HOBOKEN 07030-5774, NJ USA | |
dcterms.isPartOf.abbreviation | Embo J. | |
dcterms.oaStatus | Green Published, hybrid | |
crisitem.author.dept | Sonderforschungsbereich 944: Physiologie und Dynamik zellulärer Mikrokompartimente | - |
crisitem.author.deptid | organisation19 | - |
crisitem.author.orcid | 0000-0001-8307-2189 | - |
crisitem.author.parentorg | FB 05 - Biologie/Chemie | - |
crisitem.author.grandparentorg | Universität Osnabrück | - |
crisitem.author.netid | FrFl166 | - |
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geprüft am 29.05.2024