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Publication : Genetic analysis of synaptotagmin 2 in spontaneous and Ca2+-triggered neurotransmitter release.

First Author  Pang ZP Year  2006
Journal  EMBO J Volume  25
Issue  10 Pages  2039-50
PubMed ID  16642042 Mgi Jnum  J:108786
Mgi Id  MGI:3624891 Doi  10.1038/sj.emboj.7601103
Citation  Pang ZP, et al. (2006) Genetic analysis of synaptotagmin 2 in spontaneous and Ca(2+)-triggered neurotransmitter release. EMBO J 25(10):2039-50
abstractText  Synaptotagmin 2 resembles synaptotagmin 1, the Ca(2+) sensor for fast neurotransmitter release in forebrain synapses, but little is known about synaptotagmin 2 function. Here, we describe a severely ataxic mouse strain that harbors a single, destabilizing amino-acid substitution (I377N) in synaptotagmin 2. In Calyx of Held synapses, this mutation causes a delay and a decrease in Ca(2+)-induced but not in hypertonic sucrose-induced release, suggesting that synaptotagmin 2 mediates Ca(2+) triggering of evoked release in brainstem synapses. Unexpectedly, we additionally observed in synaptotagmin 2 mutant synapses a dramatic increase in spontaneous release. Synaptotagmin 1-deficient excitatory and inhibitory cortical synapses also displayed a large increase in spontaneous release, demonstrating that this effect was shared among synaptotagmins 1 and 2. Our data suggest that synaptotagmin 1 and 2 perform equivalent functions in the Ca(2+) triggering of action potential-induced release and in the restriction of spontaneous release, consistent with a general role of synaptotagmins in controlling 'release slots' for synaptic vesicles at the active zone.
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