Wrobel, Antoni G. ORCID: 0000-0002-6680-5587, Kadlecova, Zuzana, Kamenicky, Jan, Yang, Ji-Chun, Herrmann, Torsten ORCID: 0000-0003-2115-4781, Kelly, Bernard T., Mccoy, Airlie J., Evans, Philip R., Martin, Stephen, Mueller, Stefan, Sroubek, Filip ORCID: 0000-0001-6835-4911, Neuhaus, David, Honing, Stefan and Owen, David J. (2019). Temporal Ordering in Endocytic Clathrin-Coated Vesicle Formation via AP2 Phosphorylation. Dev. Cell, 50 (4). S. 494 - 520. CAMBRIDGE: CELL PRESS. ISSN 1878-1551

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Abstract

Clathrin-mediated endocytosis (CME) is key to maintaining the transmembrane protein composition of cells' limiting membranes. During mammalian CME, a reversible phosphorylation event occurs on Thr156 of the p2 subunit of the main endocytic clathrin adaptor, AP2. We show that this phosphorylation event starts during clathrin-coated pit (CCP) initiation and increases throughout CCP lifetime. mu 2Thr156 phosphorylation favors a new, cargo-bound conformation of AP2 and simultaneously creates a binding platform for the endocytic NECAP proteins but without significantly altering AP2's cargo affinity in vitro. We describe the structural bases of both. NECAP arrival at CCPs parallels that of clathrin and increases with mu 2Thr156 phosphorylation. In turn, NECAP recruits drivers of late stages of CCP formation, including SNX9, via a site distinct from where NECAP binds AP2. Disruption of the different modules of this phosphorylation-based temporal regulatory system results in CCP maturation being delayed and/or stalled, hence impairing global rates of CME.

Item Type: Journal Article
Creators:
CreatorsEmailORCIDORCID Put Code
Wrobel, Antoni G.UNSPECIFIEDorcid.org/0000-0002-6680-5587UNSPECIFIED
Kadlecova, ZuzanaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Kamenicky, JanUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Yang, Ji-ChunUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Herrmann, TorstenUNSPECIFIEDorcid.org/0000-0003-2115-4781UNSPECIFIED
Kelly, Bernard T.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Mccoy, Airlie J.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Evans, Philip R.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Martin, StephenUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Mueller, StefanUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Sroubek, FilipUNSPECIFIEDorcid.org/0000-0001-6835-4911UNSPECIFIED
Neuhaus, DavidUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Honing, StefanUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Owen, David J.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
URN: urn:nbn:de:hbz:38-144143
DOI: 10.1016/j.devcel.2019.07.017
Journal or Publication Title: Dev. Cell
Volume: 50
Number: 4
Page Range: S. 494 - 520
Date: 2019
Publisher: CELL PRESS
Place of Publication: CAMBRIDGE
ISSN: 1878-1551
Language: English
Faculty: Unspecified
Divisions: Unspecified
Subjects: no entry
Uncontrolled Keywords:
KeywordsLanguage
NMR STRUCTURE DETERMINATION; TORSION ANGLE DYNAMICS; STRUCTURAL EXPLANATION; NOESY SPECTRA; BINDING; ADAPTER; KINASE; SUBUNIT; DOMAIN; AAK1Multiple languages
Cell Biology; Developmental BiologyMultiple languages
Refereed: Yes
URI: http://kups.ub.uni-koeln.de/id/eprint/14414

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