title: The calcineurin-dynamin 1 complex as a calcium sensor for synaptic vesicle endocytosis.
abstract: Exocytosis of synaptic vesicles is calcium-dependent, with synaptotagmin serving as the calcium sensor. Endocytosis of synaptic vesicles has also been postulated as a calcium-dependent process; however, an endocytic calcium sensor has not been found. We now report a physical association between the calcium-dependent phosphatase calcineurin and dynamin 1, a component of the synaptic endocytic machinery. The calcineurin-dynamin 1 interaction is calcium-dependent, with an EC(50) for calcium in the range of 0.1-0. 4 microM. Disruption of the calcineurin-dynamin 1 interaction inhibits clathrin-mediated endocytosis. Thus, the calcium-dependent formation of the calcineurin-dynamin 1 complex, delivered to the other endocytic coat proteins, provides a calcium-sensing mechanism that facilitates endocytosis.
authors.affiliation: Department of Neuroscience, Johns Hopkins University School of Medicine, Baltimore, Maryland 21205, USA.
authors.forename: M M
authors.initials: MM
authors.lastname: Lai
authors.forename: J J
authors.initials: JJ
authors.lastname: Hong
authors.forename: A M
authors.initials: AM
authors.lastname: Ruggiero
authors.forename: P E
authors.initials: PE
authors.lastname: Burnett
authors.forename: V I
authors.initials: VI
authors.lastname: Slepnev
authors.forename: P
authors.initials: P
authors.lastname: De Camilli
authors.forename: S H
authors.initials: SH
authors.lastname: Snyder
mesh_terms: D000818:Animals; D019703:Calcineurin / Q000378:metabolism*; D002118:Calcium / Q000378:metabolism*; D002966:Clathrin / Q000037:antagonists & inhibitors / Q000378:metabolism; D034284:Dynamin I; D034281:Dynamins; D004705:Endocytosis; D020558:GTP Phosphohydrolases / Q000378:metabolism*; D005982:Glutathione Transferase / Q000378:metabolism; D006801:Humans; D020104:Immunophilins / Q000378:metabolism; D051381:Rats; D011993:Recombinant Fusion Proteins / Q000378:metabolism; D013572:Synaptic Vesicles / Q000378:metabolism*; D022021:Tacrolimus Binding Proteins
chemical_list: D002966:Clathrin; D011993:Recombinant Fusion Proteins; D005982:Glutathione Transferase; D019703:Calcineurin; D034284:Dynamin I; D020558:GTP Phosphohydrolases; D034281:Dynamins; D022021:Tacrolimus Binding Proteins; D020104:Immunophilins; D002118:Calcium