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  FCHO controls AP2's initiating role in endocytosis through a Ptdlns(4,5)P-2-dependent switch

Zaccai, N. R., Kadlecova, Z., Dickson, V. K., Korobchevskaya, K., Kamenicky, J., Kovtun, O., et al. (2022). FCHO controls AP2's initiating role in endocytosis through a Ptdlns(4,5)P-2-dependent switch. Science Advances, 8(17): eahn2018. doi:10.1126/sciadv.abn2018.

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 Creators:
Zaccai, Nathan R.1, Author
Kadlecova, Zuzana1, Author
Dickson, Veronica Kane1, Author
Korobchevskaya, Kseniya1, Author
Kamenicky, Jan1, Author
Kovtun, Oleksiy1, Author
Umasankar, Perunthottathu K.1, Author
Wrobel, Antoni G.1, Author
Kaufman, Jonathan G. G.1, Author
Gray, Sally R.1, Author
Qu, Kun1, Author
Evans, Philip R.1, Author
Fritzsche, Marco1, Author
Sroubek, Filip1, Author
Hoening, Stefan1, Author
Briggs, John A. G.2, Author           
Kelly, Bernard T.1, Author
Owen, David J.1, Author
Traub, Linton M.1, Author
Affiliations:
1external, ou_persistent22              
2Briggs, John / Cell and Virus Structure, Max Planck Institute of Biochemistry, Max Planck Society, ou_3344661              

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Free keywords: CLATHRIN-MEDIATED ENDOCYTOSIS; LOW-DENSITY-LIPOPROTEIN; PARTICLE CRYO-EM; CRYOELECTRON TOMOGRAPHY; STRUCTURAL EXPLANATION; MEMBRANE RECRUITMENT; ACCESSORY PROTEINS; RESOLUTION; ADAPTER; MICROSCOPYScience & Technology - Other Topics;
 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.

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Language(s): eng - English
 Dates: 2022
 Publication Status: Published online
 Pages: 21
 Publishing info: -
 Table of Contents: -
 Rev. Type: Peer
 Identifiers: ISI: 000790076700033
DOI: 10.1126/sciadv.abn2018
 Degree: -

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Title: Science Advances
  Other : Sci. Adv.
Source Genre: Journal
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Publ. Info: Washington : AAAS
Pages: - Volume / Issue: 8 (17) Sequence Number: eahn2018 Start / End Page: - Identifier: ISSN: 2375-2548
CoNE: https://pure.mpg.de/cone/journals/resource/2375-2548