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. 2016 Sep 13;16(11):2901-2913.
doi: 10.1016/j.celrep.2016.08.020.

SAD-B Phosphorylation of CAST Controls Active Zone Vesicle Recycling for Synaptic Depression

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SAD-B Phosphorylation of CAST Controls Active Zone Vesicle Recycling for Synaptic Depression

Sumiko Mochida et al. Cell Rep. .
Free article

Abstract

Short-term synaptic depression (STD) is a common form of activity-dependent plasticity observed widely in the nervous system. Few molecular pathways that control STD have been described, but the active zone (AZ) release apparatus provides a possible link between neuronal activity and plasticity. Here, we show that an AZ cytomatrix protein CAST and an AZ-associated protein kinase SAD-B coordinately regulate STD by controlling reloading of the AZ with release-ready synaptic vesicles. SAD-B phosphorylates the N-terminal serine (S45) of CAST, and S45 phosphorylation increases with higher firing rate. A phosphomimetic CAST (S45D) mimics CAST deletion, which enhances STD by delaying reloading of the readily releasable pool (RRP), resulting in a pool size decrease. A phosphonegative CAST (S45A) inhibits STD and accelerates RRP reloading. Our results suggest that the CAST/SAD-B reaction serves as a brake on synaptic transmission by temporal calibration of activity and synaptic depression via RRP size regulation.

Keywords: phosphorylation; presynaptic active zone; short-term plasticity; sympathetic neuron; synaptic vesicle.

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