Warning: file_get_contents(https://eutils.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&id=25520322
&cmd=llinks): Failed to open stream: HTTP request failed! HTTP/1.1 429 Too Many Requests
in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 215
Vesicle uncoating regulated by SH3-SH3 domain-mediated complex formation between
endophilin and intersectin at synapses
#MMPMID25520322
Pechstein A
; Gerth F
; Milosevic I
; Jäpel M
; Eichhorn-Grünig M
; Vorontsova O
; Bacetic J
; Maritzen T
; Shupliakov O
; Freund C
; Haucke V
EMBO Rep
2015[Feb]; 16
(2
): 232-9
PMID25520322
show ga
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 SH3B domain of intersectin to a non-canonical site on the SH3 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.
|Acyltransferases/genetics/metabolism
[MESH]
|Adaptor Proteins, Signal Transducing/genetics/metabolism
[MESH]
free
free
free
