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Title: FCHO controls AP2's initiating role in endocytosis through a PtdIns(4,5)P2-dependent switch.
Authors: Zaccai, Nathan R
Kadlecova, Zuzana
Dickson, Veronica Kane
Korobchevskaya, Kseniya
Kamenicky, Jan
Kovtun, Oleksiy
Umasankar, Perunthottathu K
Wrobel, Antoni G
Kaufman, Jonathan GG
Gray, Sally R
Qu, Kun 
Evans, Philip R
Fritzsche, Marco
Sroubek, Filip
Höning, Stefan
Briggs, John AG
Kelly, Bernard T
Owen, David J
Traub, Linton M
Issue Date: 29-Apr-2022
Publisher: American Association for the Advancement of Science (AAAS)
Citation: Zaccai, Nathan R, Kadlecova, Zuzana, Dickson, Veronica Kane, Korobchevskaya, Kseniya, Kamenicky, Jan, Kovtun, Oleksiy, Umasankar, Perunthottathu K, Wrobel, Antoni G, Kaufman, Jonathan GG, Gray, Sally R, Qu, Kun, Evans, Philip R, Fritzsche, Marco, Sroubek, Filip, Höning, Stefan, Briggs, John AG, Kelly, Bernard T, Owen, David J, Traub, Linton M (2022-04-29). FCHO controls AP2's initiating role in endocytosis through a PtdIns(4,5)P2-dependent switch.. Science Advances 8 (17) : eabn2018-. ScholarBank@NUS Repository.
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-localized Fer/Cip4 homology domain-only proteins (FCHO). Here, live-cell enhanced total internal reflection fluorescence-structured illumination microscopy 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/Epidermal growth factor potential receptor substrate number 15 (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 phosphatidylinositol 4,5-bisphosphate, 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.
Source Title: Science Advances
ISSN: 2375-2548
DOI: 10.1126/sciadv.abn2018
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