The calcineurin-dynamin 1 complex as a calcium sensor for synaptic vesicle endocytosis.
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.
Lai
M M
MM
Department of Neuroscience, Johns Hopkins University School of Medicine, Baltimore, Maryland 21205, USA.
Hong
J J
JJ
Ruggiero
A M
AM
Burnett
P E
PE
Slepnev
V I
VI
De Camilli
P
P
Snyder
S H
SH
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
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