Synaptotagmin-2 Is Essential for Survival and Contributes to Ca2+ Triggering of Neurotransmitter Release in Central and Neuromuscular Synapses

摘要: Biochemical and genetic data suggest that synaptotagmin-2 functions as a Ca2+ sensor for fast neurotransmitter release in caudal brain regions, but animals and/or synapses lacking have not been examined. We now generated mice which the 5' end of gene was replaced by lacZ. Using beta-galactosidase marker, we show that, consistent with previous studies, is widely expressed spinal cord, brainstem, cerebellum, additionally present selected forebrain neurons, including most striatal neurons some hypothalamic, cortical, hippocampal neurons. Synaptotagmin-2-deficient were indistinguishable from wild-type littermates at birth, subsequently developed severe motor dysfunction, perished approximately 3 weeks age. Electrophysiological studies cultured revealed deletion slowed kinetics evoked without altering total amount release. In contrast, synaptotagmin-2-deficient neuromuscular junctions (NMJs) suffered large reduction changes short-term synaptic plasticity. Furthermore, mutant NMJs, frequency spontaneous miniature events increased both rest during stimulus trains. Viewed together, our results demonstrate deficiency causes lethal impairment transmission synapses. This impairment, however, less than produced synaptotagmin-1, presumably because least synaptotagmin-1 coexpressed synaptotagmin-2, together mediate Ca2+-triggered Thus, an essential synaptotagmin isoform concert other synaptotagmins triggering