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Publication : Synaptotagmin increases the dynamic range of synapses by driving Ca²+-evoked release and by clamping a near-linear remaining Ca²+ sensor.

First Author  Kochubey O Year  2011
Journal  Neuron Volume  69
Issue  4 Pages  736-48
PubMed ID  21338883 Mgi Jnum  J:174744
Mgi Id  MGI:5140687 Doi  10.1016/j.neuron.2011.01.013
Citation  Kochubey O, et al. (2011) Synaptotagmin increases the dynamic range of synapses by driving Ca(2)+-evoked release and by clamping a near-linear remaining Ca(2)+ sensor. Neuron 69(4):736-48
abstractText  Ca(2)+-evoked transmitter release shows a high dynamic range over spontaneous release. We investigated the role of the Ca(2)+ sensor protein, Synaptotagmin2 (Syt2), in both spontaneous and Ca(2)+-evoked release under direct control of presynaptic [Ca(2)+](i), using an in vivo rescue approach at the calyx of Held. Re-expression of Syt2 rescued the highly Ca(2)+ cooperative release and suppressed the elevated spontaneous release seen in Syt2 KO synapses. This latter release clamping function was partially mediated by the poly-lysine motif of the CB domain. Using an aspartate mutation in the CB domain (D364N) in which Ca(2)+ triggering was abolished but release clamping remained intact, we show that Syt2 strongly suppresses the action of another, near-linear Ca(2)+ sensor that mediates release over a wide range of [Ca(2)+](i). Thus, Syt2 increases the dynamic range of synapses by driving release with a high Ca(2)+ cooperativity, as well as by suppressing a remaining, near-linear Ca(2)+ sensor.
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