FCHO controls AP2’s critical endocytic roles through a PtdIns4,5P<sub>2</sub> membrane-dependent switch-Reference-Cited by-同舟云学术

FCHO controls AP2’s critical endocytic roles through a PtdIns4,5P₂ membrane-dependent switch

Published:2022-04-03 Issue: Volume: Page:
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Zaccai Nathan R.^ORCID,Kadlecova Zuzana^ORCID,Dickson Veronica Kane^ORCID,Korobchevskaya Kseniya^ORCID,Kamenicky Jan,Kovtun Oleksiy^ORCID,Umasankar Perunthottathu K.^ORCID,Wrobel Antoni G.^ORCID,Kaufman Jonathan G.G.^ORCID,Gray Sally,Qu Kun^ORCID,Evans Philip R.,Fritzsche Marco^ORCID,Sroubek Filip^ORCID,Höning Stefan,Briggs John A.G.^ORCID,Kelly Bernard T.,Owen David J.^ORCID,Traub Linton M.^ORCID

Abstract

AbstractClathrin-mediated endocytosis (CME) is the main mechanism by which mammalian cells control their cell surface proteome. Proper operation of the pivotal CME cargo-adaptor AP2 requires membrane-localised FCHO. Here, live-cell eTIRF-SIM shows that FCHO marks sites of clathrin- coated pit (CCP) initiation, which mature into uniform sized CCPs comprising a central patch of AP2 and clathrin corralled by an FCHO/Eps15 ring. We dissect the network of interactions between the FCHO interdomain-linker and AP2, which concentrates, orients, tethers and partially destabilizes closed AP2 at the plasma membrane. AP2’s subsequent membrane deposition drives its opening, which triggers FCHO displacement through steric competition with PtdIns4,5P2, clathrin, cargo and CME accessory factors. FCHO can now relocate toward a CCP’s outer edge to engage and activate further AP2s to drive CCP growth/maturation.125 character summaryFCHO primes AP2 for CCV incorporation, a process that triggers FCHO release to enable activation/recruitment of further AP2s

Publisher

Cold Spring Harbor Laboratory

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