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.



Gene Ontology Annotations    Click to see Annotation Detail View

Biological Process

  
Object SymbolSpeciesTermQualifierEvidenceWithNotesSourceOriginal Reference(s)
Calm1Ratestablishment of protein localization to membrane involved_inIMP PMID:23792689CAFA 
Calm2Ratestablishment of protein localization to membrane involved_inIMP PMID:23792689CAFA 
Calm3Ratestablishment of protein localization to membrane involved_inIMP PMID:23792689CAFA 
Calm1Ratestablishment of protein localization to mitochondrial membrane involved_inIMP PMID:23792689CAFA 
Calm2Ratestablishment of protein localization to mitochondrial membrane involved_inIMP PMID:23792689CAFA 
Calm3Ratestablishment of protein localization to mitochondrial membrane involved_inIMP PMID:23792689CAFA 
Dnm1lRatnegative regulation of mitochondrial fusion involved_inIMP PMID:23792689CAFA 
Bcl2l1Ratpositive regulation of ATP biosynthetic process involved_inIMP PMID:23792689CAFA 
Bcl2l1Ratpositive regulation of synaptic vesicle clustering involved_inIMP PMID:23792689CAFA 
Bcl2l1Ratpositive regulation of synaptic vesicle endocytosis involved_inIMP PMID:23792689CAFA 
Dnm1lRatpositive regulation of synaptic vesicle endocytosis involved_inIMP PMID:23792689CAFA 
MffRatpositive regulation of synaptic vesicle endocytosis involved_inIMP PMID:23792689CAFA 
Bcl2l1Ratpositive regulation of synaptic vesicle exocytosis involved_inIMP PMID:23792689CAFA 
Dnm1lRatpositive regulation of synaptic vesicle exocytosis involved_inIMP PMID:23792689CAFA 
MffRatprotein targeting to mitochondrion involved_inIMP PMID:23792689CAFA 
Bcl2l1Ratregulation of long-term synaptic depression involved_inIMP PMID:23792689CAFA 
Bcl2l1Ratregulation of synaptic vesicle endocytosis involved_inIDA PMID:23792689SynGO 
Bcl2l1Ratregulation of synaptic vesicle endocytosis involved_inIEP PMID:23792689SynGO 
Bcl2l1Ratregulation of synaptic vesicle endocytosis involved_inIMP PMID:23792689SynGO 
Calm1Ratregulation of synaptic vesicle endocytosis involved_inIMP PMID:23792689CAFA 
Calm2Ratregulation of synaptic vesicle endocytosis involved_inIMP PMID:23792689CAFA 
Calm3Ratregulation of synaptic vesicle endocytosis involved_inIMP PMID:23792689CAFA 
Calm1Ratregulation of synaptic vesicle exocytosis involved_inIMP PMID:23792689CAFA 
Calm2Ratregulation of synaptic vesicle exocytosis involved_inIMP PMID:23792689CAFA 
Calm3Ratregulation of synaptic vesicle exocytosis involved_inIMP PMID:23792689CAFA 
Dnm1lRatsynaptic vesicle endocytosis involved_inIMP PMID:23792689SynGO 
Dnm1lRatsynaptic vesicle endocytosis involved_inIDA PMID:23792689SynGO 
Bcl2l1Ratsynaptic vesicle recycling via endosome involved_inIMP PMID:23792689CAFA 
Dnm1lRatsynaptic vesicle recycling via endosome involved_inIMP PMID:23792689CAFA 

Cellular Component

  
Object SymbolSpeciesTermQualifierEvidenceWithNotesSourceOriginal Reference(s)
Bcl2l1Ratclathrin-coated pit located_inIDA PMID:23792689CAFA 
Dnm1lRatclathrin-coated pit located_inIDA PMID:23792689CAFA 
Bcl2l1Ratmitochondrial membrane located_inIDA PMID:23792689CAFA 
Calm1Ratmitochondrial membrane located_inIMP PMID:23792689CAFA 
Calm2Ratmitochondrial membrane located_inIMP PMID:23792689CAFA 
Calm3Ratmitochondrial membrane located_inIMP PMID:23792689CAFA 
Dnm1lRatmitochondrial membrane located_inIDA PMID:23792689CAFA 
MffRatmitochondrial membrane located_inIMP PMID:23792689CAFA 
Bcl2l1Ratpresynapse located_inIDA PMID:23792689CAFA 
Dnm1lRatpresynaptic endocytic zone membrane is_active_inIDA PMID:23792689SynGO 
Bcl2l1Ratsynaptic vesicle is_active_inIDA PMID:23792689SynGO 
MffRatsynaptic vesicle  IDA  RGD 
Bcl2l1Ratsynaptic vesicle membrane located_inIDA PMID:23792689CAFA 
Calm1Ratsynaptic vesicle membrane located_inIMP PMID:23792689CAFA 
Calm2Ratsynaptic vesicle membrane located_inIMP PMID:23792689CAFA 
Calm3Ratsynaptic vesicle membrane located_inIMP PMID:23792689CAFA 
CltaRatsynaptic vesicle membrane located_inIDA PMID:23792689CAFA 
Dnm1lRatsynaptic vesicle membrane is_active_inIDA PMID:23792689SynGO 
MffRatsynaptic vesicle membrane located_inIMP PMID:23792689CAFA 
SypRatsynaptic vesicle membrane located_inIDA PMID:23792689CAFA 
Syt1Ratsynaptic vesicle membrane located_inIDA PMID:23792689CAFA 
Vamp2Ratsynaptic vesicle membrane located_inIDA PMID:23792689CAFA 

Molecular Function

  
Object SymbolSpeciesTermQualifierEvidenceWithNotesSourceOriginal Reference(s)
Dnm1lRatBH2 domain binding enablesIPIUniProtKB:P53563PMID:23792689CAFA 
Bcl2l1Ratclathrin binding enablesIPIUniProtKB:P08081PMID:23792689CAFA 
Dnm1lRatclathrin binding enablesIPIUniProtKB:P08081PMID:23792689CAFA 
Bcl2l1RatGTPase binding enablesIPIUniProtKB:O35303PMID:23792689CAFA 
CltaRatGTPase binding enablesIPIUniProtKB:O35303PMID:23792689CAFA 
MffRatGTPase binding  IPIDnm1l (Rattus norvegicus) RGD 
MffRatGTPase binding enablesIPIUniProtKB:O35303PMID:23792689CAFA 
Bcl2l1Ratprotein binding enablesIPIUniProtKB:O35303PMID:23792689IntAct 
Bcl2l1Ratprotein binding enablesIPIUniProtKB:P08081PMID:23792689IntAct 
Bcl2l1Ratprotein binding enablesIPIUniProtKB:Q4KM98PMID:23792689CAFA 
CltaRatprotein binding enablesIPIUniProtKB:P53563PMID:23792689CAFA 
CltaRatprotein binding enablesIPIUniProtKB:P53563-1PMID:23792689IntAct 
Dnm1lRatprotein binding enablesIPIUniProtKB:P53563-1PMID:23792689IntAct 
Dnm1lRatprotein binding enablesIPIUniProtKB:Q4KM98PMID:23792689CAFA 
MffRatprotein binding enablesIPIUniProtKB:P21707PMID:23792689CAFA 
MffRatprotein binding enablesIPIUniProtKB:P53563PMID:23792689CAFA 
Syt1Ratprotein binding enablesIPIUniProtKB:Q4KM98PMID:23792689CAFA 
Bcl2l1Ratprotein-containing complex binding  IPIRGD:1310230|RGD:620416|RGD:70919 RGD 
CltaRatprotein-containing complex binding  IPIRGD:1310230|RGD:2200|RGD:620416 RGD 
Dnm1lRatprotein-containing complex binding  IPIRGD:1310230|RGD:2200|RGD:70919 RGD 
MffRatprotein-containing complex binding  IPIRGD:2200|RGD:620416|RGD:70919 RGD 

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