Neurons contact each other mostly by synaptic transmission at synapses. The maintenance of synaptic transmission relies on vesicle endocytosis, which recycles fused vesicles for the second round of exocytosis. My goal is to improve our understanding on the cellular and molecular mechanisms underlying synaptic vesicle endocytosis, which are the building block for the maintenance of synaptic transmission and thus the signaling process of the nervous system. My progress in the last year is listed in the following. First, although endocytosis is crucial for recycling and maintaining synaptic transmission, how it is initiated and controlled are poorly understood. We found that all forms of endocytosis are initiated by calcium influx (Wu et al., Nature Neurosci, 2009). The caclium sensor mediating calcium-triggered endocytosis is calmodulin. These findings resolve a long-held puzzle in the field of endocytosis, i.e., the initiation of endocytosis. They also provide an unifying mechanism explaining various forms, amounts and rates of endocytosis observed in many cell-types over the last three decades. Second, the widely observed rapid endocytosis is generally assumed to recycle vesicles within the readily releasable pool (RRP) via a kiss-and-run mechanism that involves rapid opening and closure of a fusion pore at the release site. Here we found that rapid endocytosis do not recycle vesicles to the RRP, but to a large recycling pool (Wu &Wu, J Neurosci, 2009). We suggest that rapid endocytosis provides the nerve terminal the ability to recycle vesicles rapidly via the recycling pool, and to maintain the normal morphology of the nerve terminal, including the release site, by rapidly clearing the fused vesicle membrane from the release site during intense firing. Third, we provided an up-to-date review on the subjects of endocytosis in two book chapters (He et al., 2008;Zimmerberg et al., 2008).
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