title: Synaptic vesicle endocytosis impaired by disruption of dynamin-SH3 domain interactions.
abstract: The proline-rich COOH-terminal region of dynamin binds various Src homology 3 (SH3) domain-containing proteins, but the physiological role of these interactions is unknown. In living nerve terminals, the function of the interaction with SH3 domains was examined. Amphiphysin contains an SH3 domain and is a major dynamin binding partner at the synapse. Microinjection of amphiphysin's SH3 domain or of a dynamin peptide containing the SH3 binding site inhibited synaptic vesicle endocytosis at the stage of invaginated clathrin-coated pits, which resulted in an activity-dependent distortion of the synaptic architecture and a depression of transmitter release. These findings demonstrate that SH3-mediated interactions are required for dynamin function and support an essential role of clathrin-mediated endocytosis in synaptic vesicle recycling.
authors.affiliation: The Nobel Institute for Neurophysiology, Department of Neuroscience, Karolinska Institutet, S-171 77 Stockholm, Sweden.
authors.forename: O
authors.initials: O
authors.lastname: Shupliakov
authors.forename: P
authors.initials: P
authors.lastname: Löw
authors.forename: D
authors.initials: D
authors.lastname: Grabs
authors.forename: H
authors.initials: H
authors.lastname: Gad
authors.forename: H
authors.initials: H
authors.lastname: Chen
authors.forename: C
authors.initials: C
authors.lastname: David
authors.forename: K
authors.initials: K
authors.lastname: Takei
authors.forename: P
authors.initials: P
authors.lastname: De Camilli
authors.forename: L
authors.initials: L
authors.lastname: Brodin
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D001665:Binding Sites; D002462:Cell Membrane / Q000648:ultrastructure; D003034:Coated Pits, Cell-Membrane / Q000648:ultrastructure; D034281:Dynamins; D004705:Endocytosis; D020558:GTP Phosphohydrolases / Q000378:metabolism*; D006801:Humans; D007798:Lampreys; D008854:Microscopy, Electron; D008969:Molecular Sequence Data; D009419:Nerve Tissue Proteins / Q000737:chemistry / Q000378:metabolism*; D011392:Proline / Q000737:chemistry; D011993:Recombinant Fusion Proteins / Q000378:metabolism; D013569:Synapses / Q000378:metabolism / Q000648:ultrastructure; D009435:Synaptic Transmission; D013572:Synaptic Vesicles / Q000378:metabolism* / Q000648:ultrastructure; D018909:src Homology Domains
chemical_list: D009419:Nerve Tissue Proteins; D011993:Recombinant Fusion Proteins; C075637:amphiphysin; D011392:Proline; D020558:GTP Phosphohydrolases; D034281:Dynamins