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Temporal Ordering in Endocytic Clathrin-Coated Vesicle Formation via AP2 Phosphorylation

AG. Wrobel, Z. Kadlecova, J. Kamenicky, JC. Yang, T. Herrmann, BT. Kelly, AJ. McCoy, PR. Evans, S. Martin, S. Müller, S. Salomon, F. Sroubek, D. Neuhaus, S. Höning, DJ. Owen,

. 2019 ; 50 (4) : 494-508.e11. [pub] 20190819

Jazyk angličtina Země Spojené státy americké

Typ dokumentu časopisecké články, práce podpořená grantem

Perzistentní odkaz   https://www.medvik.cz/link/bmc20023740

Grantová podpora
Wellcome Trust - United Kingdom
MC_U105178845 Medical Research Council - United Kingdom
MC_U105178934 Medical Research Council - United Kingdom
090909/Z/09/Z Wellcome Trust - United Kingdom
097040/Z/11/Z Wellcome Trust - United Kingdom

E-zdroje Online Plný text

NLK Cell Press Free Archives od 2001-07-01 do Před 1 rokem
Free Medical Journals od 2001 do Před 1 rokem
Elsevier Open Access Journals od 2001-07-01 do 2023-06-19
Elsevier Open Archive Journals od 2001-07-01 do Před 1 rokem

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 μ2 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. μ2Thr156 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 μ2Thr156 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.

Citace poskytuje Crossref.org

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