Kinetic efficiency of endocytosis at mammalian CNS synapses requires synaptotagmin I

At nerve terminals, synaptic vesicle components are retrieved from the cell surface and recycled for local reuse soon after exocytosis. The kinetics of this coupling is critical for the proper functioning of synapses during repetitive action potential firing, because deficiencies in this process lead to abnormal depletion of the releasable vesicle pool. Although the molecular basis of this coupling is poorly understood, numerous biochemical data point to a role for synaptotagmin I (SytI), an essential synaptic vesicle protein required for fast calcium-dependent exocytosis. Here, using synapto-pHluorin in an approach that allows the dissection of endocytosis and exocytosis into separate components during periods of stimulation, we examined exocytic-endocytic coupling in synapses from Sytl knockout mice and their WT littermates. We show that endocytosis is significantly impaired in the absence of Sytl with the relative rates of endocytosis compared with exocytosis reduced approximate to3-fold with respect to WT. Thus, in addition to regulating exocytosis, Sytl also controls the kinetic efficiency of endocytosis at nerve terminals.