RGD Reference Report - A Bcl-xL-Drp1 complex regulates synaptic vesicle membrane dynamics during endocytosis. - Rat Genome Database

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A Bcl-xL-Drp1 complex regulates synaptic vesicle membrane dynamics during endocytosis.

Authors: Li, Hongmei  Alavian, Kambiz N  Lazrove, Emma  Mehta, Nabil  Jones, Adrienne  Zhang, Ping  Licznerski, Pawel  Graham, Morven  Uo, Takuma  Guo, Junhua  Rahner, Christoph  Duman, Ronald S  Morrison, Richard S  Jonas, Elizabeth A 
Citation: Li H, etal., Nat Cell Biol. 2013 Jul;15(7):773-85. doi: 10.1038/ncb2791. Epub 2013 Jun 23.
RGD ID: 12793033
Pubmed: PMID:23792689   (View Abstract at PubMed)
PMCID: PMC3725990   (View Article at PubMed Central)
DOI: DOI:10.1038/ncb2791   (Journal Full-text)

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.

Objects Annotated

Genes (Rattus norvegicus)
Bcl2l1  (Bcl2-like 1)
Calm1  (calmodulin 1)
Calm2  (calmodulin 2)
Calm3  (calmodulin 3)
Clta  (clathrin, light chain A)
Dnm1l  (dynamin 1-like)
Mff  (mitochondrial fission factor)
Syp  (synaptophysin)
Syt1  (synaptotagmin 1)
Vamp2  (vesicle-associated membrane protein 2)

Additional Information