Exocytosis of synaptic vesicles is calcium-dependent, with synaptotagmin se
rving as the calcium sensor. Endocytosis of synaptic vesicles has also been
postulated as a calcium-dependent process; however, an endocytic calcium s
ensor 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 cal
cium-dependent, with an EC50 for calcium in the range of 0.1-0.4 mu M. Disr
uption of the calcineurin-dynamin 1 interaction inhibits clathrin-mediated
endocytosis. Thus, the calcium-dependent formation of the calcineurin-dynam
in 1 complex, delivered to the other endocytic coat proteins, provides a ca
lcium-sensing mechanism that facilitates endocytosis.