FCHO controls AP2’s initiating role in endocytosis through a PtdIns4,5P2 -dependent switch
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Authors
Zaccai, Nathan
Kadlecova, Zuzana
Jonathan, Kaufman
Sally, Gray
Bernard, Kelly
Publication Date
2022-04-29Journal Title
Science Advances
ISSN
2375-2548
Publisher
American Association for the Advancement of Science
Volume
8
Issue
17
Language
eng
Type
Article
This Version
VoR
Metadata
Show full item recordCitation
Owen, D., Zaccai, N., Kadlecova, Z., Kane Dickson, V., Jonathan, K., Sally, G., & Bernard, K. (2022). FCHO controls AP2’s initiating role in endocytosis through a PtdIns4,5P2 -dependent switch. Science Advances, 8 (17) https://doi.org/10.1126/sciadv.abn2018
Abstract
Clathrin-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.
Keywords
2 Aetiology, 1.1 Normal biological development and functioning, 2.1 Biological and endogenous factors, 1 Underpinning research, Generic health relevance
Sponsorship
Wellcome Trust (202905/Z/16/Z)
Wellcome Trust (207455/Z/17/Z)
Identifiers
35486718, PMC9054013
External DOI: https://doi.org/10.1126/sciadv.abn2018
This record's URL: https://www.repository.cam.ac.uk/handle/1810/337807
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