Zaccai, Nathan R., Kadlecova, Zuzana ORCID: 0000-0001-6335-1105, Dickson, Veronica Kane, Korobchevskaya, Kseniya, Kamenicky, Jan, Kovtun, Oleksiy ORCID: 0000-0001-6374-7863, Umasankar, Perunthottathu K., Wrobel, Antoni G. ORCID: 0000-0002-6680-5587, Kaufman, Jonathan G. G., Gray, Sally R., Qu, Kun, Evans, Philip R., Fritzsche, Marco, Sroubek, Filip ORCID: 0000-0001-6835-4911, Hoening, Stefan, Briggs, John A. G., Kelly, Bernard T., Owen, David J. and Traub, Linton M. (2022). FCHO controls AP2's initiating role in endocytosis through a Ptdlns(4,5)P-2-dependent switch. Sci. Adv., 8 (17). WASHINGTON: AMER ASSOC ADVANCEMENT SCIENCE. ISSN 2375-2548

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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.

Item Type: Journal Article
Creators:
CreatorsEmailORCIDORCID Put Code
Zaccai, Nathan R.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Kadlecova, ZuzanaUNSPECIFIEDorcid.org/0000-0001-6335-1105UNSPECIFIED
Dickson, Veronica KaneUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Korobchevskaya, KseniyaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Kamenicky, JanUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Kovtun, OleksiyUNSPECIFIEDorcid.org/0000-0001-6374-7863UNSPECIFIED
Umasankar, Perunthottathu K.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Wrobel, Antoni G.UNSPECIFIEDorcid.org/0000-0002-6680-5587UNSPECIFIED
Kaufman, Jonathan G. G.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Gray, Sally R.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Qu, KunUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Evans, Philip R.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Fritzsche, MarcoUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Sroubek, FilipUNSPECIFIEDorcid.org/0000-0001-6835-4911UNSPECIFIED
Hoening, StefanUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Briggs, John A. G.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Kelly, Bernard T.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Owen, David J.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Traub, Linton M.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
URN: urn:nbn:de:hbz:38-692251
DOI: 10.1126/sciadv.abn2018
Journal or Publication Title: Sci. Adv.
Volume: 8
Number: 17
Date: 2022
Publisher: AMER ASSOC ADVANCEMENT SCIENCE
Place of Publication: WASHINGTON
ISSN: 2375-2548
Language: English
Faculty: Unspecified
Divisions: Unspecified
Subjects: no entry
Uncontrolled Keywords:
KeywordsLanguage
CLATHRIN-MEDIATED ENDOCYTOSIS; LOW-DENSITY-LIPOPROTEIN; PARTICLE CRYO-EM; CRYOELECTRON TOMOGRAPHY; STRUCTURAL EXPLANATION; MEMBRANE RECRUITMENT; ACCESSORY PROTEINS; RESOLUTION; ADAPTER; MICROSCOPYMultiple languages
Multidisciplinary SciencesMultiple languages
URI: http://kups.ub.uni-koeln.de/id/eprint/69225

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