Missing-in-metastasis protein downregulates CXCR4 by promoting ubiquitylation and interaction with small Rab GTPases
JournalJournal of Cell Science
PublisherCompany of Biologists Ltd
MetadataShow full item record
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.
Identifier to cite or link to this itemhttps://www.scopus.com/inward/record.uri?eid=2-s2.0-85017542196&doi=10.1242%2fjcs.198937&partnerID=40&md5=de3ac4e41884482f909822b5cbecc3e6; http://hdl.handle.net/10713/9949