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Vesicle uncoating regulated by SH 3‐ SH 3 domain‐mediated complex formation between endophilin and intersectin at synapses
Author(s) -
Pechstein Arndt,
Gerth Fabian,
Milosevic Ira,
Jäpel Maria,
EichhornGrünig Marielle,
Vorontsova Olga,
Bacetic Jelena,
Maritzen Tanja,
Shupliakov Oleg,
Freund Christian,
Haucke Volker
Publication year - 2015
Publication title -
embo reports
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 4.584
H-Index - 184
eISSN - 1469-3178
pISSN - 1469-221X
DOI - 10.15252/embr.201439260
Subject(s) - chemistry , microbiology and biotechnology , domain (mathematical analysis) , vesicle , biophysics , biochemistry , biology , membrane , mathematical analysis , mathematics
Neurotransmission involves the exo‐endocytic cycling of synaptic vesicle ( SV ) membranes. Endocytic membrane retrieval and clathrin‐mediated SV reformation require curvature‐sensing and membrane‐bending BAR domain proteins such as endophilin A. While their ability to sense and stabilize curved membranes facilitates membrane recruitment of BAR domain proteins, the precise mechanisms by which they are targeted to specific sites of SV recycling has remained unclear. Here, we demonstrate that the multi‐domain scaffold intersectin 1 directly associates with endophilin A to facilitate vesicle uncoating at synapses. Knockout mice deficient in intersectin 1 accumulate clathrin‐coated vesicles at synapses, a phenotype akin to loss of endophilin function. Intersectin 1/endophilin A1 complex formation is mediated by direct binding of the SH 3B domain of intersectin to a non‐canonical site on the SH 3 domain of endophilin A1. Consistent with this, intersectin‐binding defective mutant endophilin A1 fails to rescue clathrin accumulation at neuronal synapses derived from endophilin A1‐3 triple knockout ( TKO ) mice. Our data support a model in which intersectin aids endophilin A recruitment to sites of clathrin‐mediated SV recycling, thereby facilitating vesicle uncoating.