Synaptophysin regulates clathrin-independent endocytosis of synaptic vesicles.
The GTPase dynamin I is required for synaptic vesicle (SV) endocytosis. Our observation that dynamin binds to the SV protein synaptophysin in a Ca(2+)-dependent fashion suggested the possibility that a dynamin/synaptophysin complex functions in SV recycling. In this paper we show that disruption of the dynamin/synaptophysin interaction by peptide injection into the squid giant synapse preterminal results in a decrease in transmitter release during high-frequency stimulation, indicating an inhibition of SV recycling. Electron microscopy of these synapses reveals a depletion of SVs, demonstrating a block of vesicle retrieval after fusion. In addition, we observed an increase in clathrin-coated vesicles, indicating that the peptide does not block clathrin-dependent endocytosis. We conclude that the dynamin/synaptophysin complex functions in a clathrin-independent mechanism of SV endocytosis that is required for efficient synaptic transmission.
Daly
C
C
Howard Hughes Medical Institute and Department of Biochemistry, New York University Medical Center, New York, NY 10016, USA.
Sugimori
M
M
Moreira
J E
JE
Ziff
E B
EB
Llinás
R
R
D000818:Animals; D002118:Calcium / Q000502:physiology; D002966:Clathrin / Q000502:physiology; D049832:Decapodiformes; D034284:Dynamin I; D034281:Dynamins; D004705:Endocytosis / Q000502:physiology*; D020558:GTP Phosphohydrolases / Q000502:physiology; D046911:Macromolecular Substances; D008561:Membrane Fusion; D009419:Nerve Tissue Proteins / Q000502:physiology*; D011993:Recombinant Fusion Proteins / Q000502:physiology; D013233:Stellate Ganglion / Q000166:cytology; D009435:Synaptic Transmission / Q000502:physiology; D013572:Synaptic Vesicles / Q000502:physiology*; D016708:Synaptophysin / Q000502:physiology*
D002966:Clathrin; D046911:Macromolecular Substances; D009419:Nerve Tissue Proteins; D011993:Recombinant Fusion Proteins; D016708:Synaptophysin; D034284:Dynamin I; D020558:GTP Phosphohydrolases; D034281:Dynamins; D002118:Calcium