The GTPase dynamin I is required for synaptic vesicle (SV) endocytosis, Our
observation that dynamin binds to the SV protein synaptophysin in a Ca2+-d
ependent fashion suggested the possibility that a dynamin/synaptophysin com
plex functions in SV recycling, In this paper we show that disruption of th
e dynamin/synaptophysin interaction by peptide injection into the squid gia
nt synapse preterminal results in a decrease in transmitter release during
high-frequency stimulation, indicating an inhibition of SV recycling, Elect
ron microscopy of these synapses reveals a depletion of SVs. demonstrating
a block of vesicle retrieval after fusion, In addition, we observed an incr
ease in clathrin-coated vesicles, indicating that the peptide does not bloc
k clathrin-dependent endocytosis, We conclude that the dynamin/synaptophysi
n complex functions in a clathrin-independent mechanism of SV endocytosis t
hat is required for efficient synaptic transmission.