title: A Bcl-xL-Drp1 complex regulates synaptic vesicle membrane dynamics during endocytosis.
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.
authors.affiliation: Department of Internal Medicine, Yale University, New Haven, Connecticut 06520, USA.
authors.forename: Hongmei
authors.initials: H
authors.lastname: Li
authors.forename: Kambiz N
authors.initials: KN
authors.lastname: Alavian
authors.forename: Emma
authors.initials: E
authors.lastname: Lazrove
authors.forename: Nabil
authors.initials: N
authors.lastname: Mehta
authors.forename: Adrienne
authors.initials: A
authors.lastname: Jones
authors.forename: Ping
authors.initials: P
authors.lastname: Zhang
authors.forename: Pawel
authors.initials: P
authors.lastname: Licznerski
authors.forename: Morven
authors.initials: M
authors.lastname: Graham
authors.forename: Takuma
authors.initials: T
authors.lastname: Uo
authors.forename: Junhua
authors.initials: J
authors.lastname: Guo
authors.forename: Christoph
authors.initials: C
authors.lastname: Rahner
authors.forename: Ronald S
authors.initials: RS
authors.lastname: Duman
authors.forename: Richard S
authors.initials: RS
authors.lastname: Morrison
authors.forename: Elizabeth A
authors.initials: EA
authors.lastname: Jonas
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D002147:Calmodulin / Q000378:metabolism; D002478:Cells, Cultured; D002966:Clathrin / Q000378:metabolism; D034281:Dynamins / Q000502:physiology*; D004705:Endocytosis / Q000502:physiology*; D006624:Hippocampus / Q000166:cytology / Q000378:metabolism*; D015151:Immunoblotting; D047468:Immunoprecipitation; D008928:Mitochondria / Q000378:metabolism; D008969:Molecular Sequence Data; D009474:Neurons / Q000166:cytology / Q000378:metabolism*; D021381:Protein Transport; D051381:Rats; D017386:Sequence Homology, Amino Acid; D013570:Synaptic Membranes / Q000502:physiology*; D009435:Synaptic Transmission; D013572:Synaptic Vesicles / Q000502:physiology*; D051020:bcl-X Protein / Q000502:physiology*
chemical_list: C494813:Bcl2l1 protein, rat; D002147:Calmodulin; D002966:Clathrin; D051020:bcl-X Protein; C519851:Dnm1l protein, rat; D034281:Dynamins