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dc.contributor.authorLi, L.
dc.contributor.authorBaxter, S.S.
dc.contributor.authorGu, N.
dc.date.accessioned2019-07-15T16:12:13Z
dc.date.available2019-07-15T16:12:13Z
dc.date.issued2017
dc.identifier.urihttps://www.scopus.com/inward/record.uri?eid=2-s2.0-85017542196&doi=10.1242%2fjcs.198937&partnerID=40&md5=de3ac4e41884482f909822b5cbecc3e6
dc.identifier.urihttp://hdl.handle.net/10713/9949
dc.description.abstractSurface expression of chemokine receptor CXCR4 is downregulated by missing-in-metastasis protein (MIM; also known as MTSS1), a member of the inverse BAR (I-BAR)-domain protein family that recognizes and generates membranes with negative curvature. Yet, the mechanism for the regulation is unknown. Here, we show that MIM forms a complex with CXCR4 by binding to E3 ubiquitin ligase AIP4 (also known as ITCH) in response to stromal cell-derived factor 1 (SDF-1; also known as CXCL12). Overexpression of MIM promoted CXCR4 ubiquitylation, inhibited cellular response to SDF-1, caused accumulation and aggregation of multivesicular bodies (MVBs) in the cytoplasm, and promoted CXCR4 sorting into MVBs in a manner depending on binding to AIP4. In response to SDF-1, MIM also bound transiently to the small GTPase Rab5 at 5 min and to Rab7 at 30 min. Binding to Rab7 requires an N-terminal coiled-coil motif, deletion of which abolished MIM-mediated MVB formation and CXCR4 internalization. Our results unveil a previously unknown property of MIM that establishes the linkage of protein ubiquitylation with Rab-guided trafficking of CXCR4 in endocytic vesicles. Copyright 2017. Published by The Company of Biologists Ltd.en_US
dc.description.urihttps://www.doi.org/10.1242/jcs.198937en_US
dc.language.isoen_USen_US
dc.publisherCompany of Biologists Ltden_US
dc.relation.ispartofJournal of Cell Science
dc.subjectAIP4en_US
dc.subjectCXCR4en_US
dc.subjectMIMen_US
dc.subjectMVBsen_US
dc.subjectRab7en_US
dc.subjectUbiquitylationen_US
dc.titleMissing-in-metastasis protein downregulates CXCR4 by promoting ubiquitylation and interaction with small Rab GTPasesen_US
dc.typeArticleen_US
dc.identifier.doi10.1242/jcs.198937
dc.identifier.pmid28264927


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