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dc.contributor.authorOwen, David
dc.contributor.authorZaccai, Nathan
dc.contributor.authorKadlecova, Zuzana
dc.contributor.authorKane Dickson, Veronica
dc.contributor.authorJonathan, Kaufman
dc.contributor.authorSally, Gray
dc.contributor.authorBernard, Kelly
dc.date.accessioned2022-06-07T08:15:30Z
dc.date.available2022-06-07T08:15:30Z
dc.date.issued2022-04-29
dc.identifier.issn2375-2548
dc.identifier.other35486718
dc.identifier.otherPMC9054013
dc.identifier.urihttps://www.repository.cam.ac.uk/handle/1810/337807
dc.description.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.
dc.languageeng
dc.publisherAmerican Association for the Advancement of Science
dc.rightsAttribution 4.0 International
dc.rights.urihttps://creativecommons.org/licenses/by/4.0/
dc.sourcenlmid: 101653440
dc.sourceessn: 2375-2548
dc.titleFCHO controls AP2’s initiating role in endocytosis through a PtdIns4,5P2 -dependent switch
dc.typeArticle
dc.date.updated2022-06-07T08:15:29Z
prism.issueIdentifier17
prism.publicationNameScience Advances
prism.volume8
dc.identifier.doi10.17863/CAM.85216
dcterms.dateAccepted2022-04-01
rioxxterms.versionofrecord10.1126/sciadv.abn2018
rioxxterms.versionVoR
rioxxterms.licenseref.urihttps://creativecommons.org/licenses/by/4.0/
dc.contributor.orcidOwen, David [0000-0002-8351-6322]
dc.contributor.orcidKane Dickson, Veronica [0000-0002-8649-8094]
dc.identifier.eissn2375-2548
pubs.funder-project-idWellcome Trust (202905/Z/16/Z)
pubs.funder-project-idWellcome Trust (207455/Z/17/Z)
cam.issuedOnline2022-04-29


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Attribution 4.0 International
Except where otherwise noted, this item's licence is described as Attribution 4.0 International