A Bcl-x(L)-Drp1 complex regulates synaptic vesicle membrane dynamics during endocytosis
Author(s)
Type
Journal Article
Abstract
Following exocytosis, the rate of recovery of neurotransmitter release is determined by vesicle retrieval from the plasma membrane and by recruitment of vesicles from reserve pools within the synapse, which is dependent on mitochondrial ATP. The anti-apoptotic Bcl-2 family protein Bcl-xL also regulates neurotransmitter release and recovery in part by increasing ATP availability from mitochondria. We now find, that Bcl-xL directly regulates endocytic vesicle retrieval in hippocampal neurons through protein–protein interaction with components of the clathrin complex. Our evidence suggests that, during synaptic stimulation, Bcl-xL translocates to clathrin-coated pits in a calmodulin-dependent manner and forms a complex with the GTPase Drp1, Mff and clathrin. Depletion of Drp1 produces misformed endocytic vesicles. Mutagenesis studies suggest that formation of the Bcl-xL–Drp1 complex is necessary for the enhanced rate of vesicle endocytosis produced by Bcl-xL, thus providing a mechanism for presynaptic plasticity.
Date Issued
2013-07-01
Date Acceptance
2013-05-20
Citation
Nature Cell Biology, 2013, 15 (7), pp.773-785
ISSN
1465-7392
Publisher
Nature Research
Start Page
773
End Page
785
Journal / Book Title
Nature Cell Biology
Volume
15
Issue
7
Identifier
https://www.webofscience.com/api/gateway?GWVersion=2&SrcApp=PARTNER_APP&SrcAuth=LinksAMR&KeyUT=WOS:000321181400010&DestLinkType=FullRecord&DestApp=ALL_WOS&UsrCustomerID=1ba7043ffcc86c417c072aa74d649202
Subjects
APOPTOSIS
BCL-X-L
Cell Biology
CYTOCHROME-C
DRP1
ENDOPHILIN
FAMILY
Life Sciences & Biomedicine
MITOCHONDRIAL FISSION
POOL
RECRUITMENT
Science & Technology
TRANSMISSION
Publication Status
Published
Date Publish Online
2013-06-23