Regulating peroxisome–ER contacts via the ACBD5-VAPB tether by FFAT motif phosphorylation and GSK3β
dc.contributor.author | Kors, S | |
dc.contributor.author | Hacker, C | |
dc.contributor.author | Bolton, C | |
dc.contributor.author | Maier, R | |
dc.contributor.author | Reimann, L | |
dc.contributor.author | Kitchener, EJA | |
dc.contributor.author | Warscheid, B | |
dc.contributor.author | Costello, JL | |
dc.contributor.author | Schrader, M | |
dc.date.accessioned | 2022-01-13T10:45:58Z | |
dc.date.issued | 2022-01-12 | |
dc.date.updated | 2022-01-12T17:49:31Z | |
dc.description.abstract | Peroxisomes and the endoplasmic reticulum (ER) cooperate in cellular lipid metabolism. They form membrane contacts through interaction of the peroxisomal membrane protein ACBD5 (acyl-coenzyme A–binding domain protein 5) and the ER-resident protein VAPB (vesicle-associated membrane protein–associated protein B). ACBD5 binds to the major sperm protein domain of VAPB via its FFAT-like (two phenylalanines [FF] in an acidic tract) motif. However, molecular mechanisms, which regulate formation of these membrane contact sites, are unknown. Here, we reveal that peroxisome–ER associations via the ACBD5-VAPB tether are regulated by phosphorylation. We show that ACBD5-VAPB binding is phosphatase-sensitive and identify phosphorylation sites in the flanking regions and core of the FFAT-like motif, which alter interaction with VAPB—and thus peroxisome–ER contact sites—differently. Moreover, we demonstrate that GSK3β (glycogen synthase kinase-3 β) regulates this interaction. Our findings reveal for the first time a molecular mechanism for the regulation of peroxisome–ER contacts in mammalian cells and expand the current model of FFAT motifs and VAP interaction. | en_GB |
dc.description.sponsorship | Biotechnology and Biological Sciences Research Council (BBSRC) | en_GB |
dc.description.sponsorship | Medical Research Council (MRC) | en_GB |
dc.description.sponsorship | UKRI | en_GB |
dc.description.sponsorship | Royal Society | en_GB |
dc.description.sponsorship | University of Exeter | en_GB |
dc.description.sponsorship | European Union Horizon 2020 | en_GB |
dc.description.sponsorship | Deutsche Forschungsgemeinschaft | en_GB |
dc.identifier.citation | Vol. 221(3), article e202003143 | en_GB |
dc.identifier.doi | https://doi.org/10.1083/jcb.202003143 | |
dc.identifier.grantnumber | BB/N01541X/1 | en_GB |
dc.identifier.grantnumber | BB/T002255/1 | en_GB |
dc.identifier.grantnumber | CiC 08135 | en_GB |
dc.identifier.grantnumber | MR/T019409/1 | en_GB |
dc.identifier.grantnumber | RGS\R2\192378 | en_GB |
dc.identifier.grantnumber | 812968 | en_GB |
dc.identifier.grantnumber | 278002225/GRK 2202 | en_GB |
dc.identifier.grantnumber | FOR 1905 | en_GB |
dc.identifier.grantnumber | 403222702 –SFB 1381 | en_GB |
dc.identifier.grantnumber | 390939984 | en_GB |
dc.identifier.grantnumber | MR/N0137941/1 | en_GB |
dc.identifier.uri | http://hdl.handle.net/10871/128389 | |
dc.identifier | ORCID: 0000-0002-2867-1864 (Costello, Joseph L) | |
dc.identifier | ScopusID: 56519271600 (Costello, Joseph L) | |
dc.identifier | ORCID: 0000-0003-2146-0535 (Schrader, Michael) | |
dc.language.iso | en | en_GB |
dc.publisher | Rockefeller University Press | en_GB |
dc.relation.url | http://proteomecentral. proteomexchange.org | en_GB |
dc.rights | © 2022 Kors et al. Open access This article is available under a Creative Commons License (Attribution 4.0 International, as described at https://creativecommons.org/licenses/by/4.0/). | en_GB |
dc.title | Regulating peroxisome–ER contacts via the ACBD5-VAPB tether by FFAT motif phosphorylation and GSK3β | en_GB |
dc.type | Article | en_GB |
dc.date.available | 2022-01-13T10:45:58Z | |
dc.identifier.issn | 0021-9525 | |
dc.description | This is the final version. Available on open access from Rockefeller University Press via the DOI in this record | en_GB |
dc.description | Data availability All raw data and original Mascot result files have been deposited to the ProteomeXchange Consortium (http://proteomecentral. proteomexchange.org) via the PRIDE partner repository (http:// www.ebi.ac.uk/pride/archive/login; Perez-Riverol et al., 2019) with the dataset identifier PXD018005. The research data supporting this publication are provided within this paper, as supplementary information, or are deposited on PRIDE. | en_GB |
dc.identifier.eissn | 1540-8140 | |
dc.identifier.journal | Journal of Cell Biology | en_GB |
dc.relation.ispartof | Journal of Cell Biology, 221(3) | |
dc.rights.uri | https://creativecommons.org/licenses/by/4.0/ | en_GB |
dcterms.dateAccepted | 2021-12-15 | |
rioxxterms.version | VoR | en_GB |
rioxxterms.licenseref.startdate | 2022-01-12 | |
rioxxterms.type | Journal Article/Review | en_GB |
refterms.dateFCD | 2022-01-13T10:40:50Z | |
refterms.versionFCD | VoR | |
refterms.dateFOA | 2022-01-13T10:46:19Z | |
refterms.panel | A | en_GB |
refterms.dateFirstOnline | 2022-01-12 |
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Except where otherwise noted, this item's licence is described as © 2022 Kors et al. Open access This article is available under a Creative Commons License (Attribution 4.0 International, as described at https://creativecommons.org/licenses/by/4.0/).