| First Author | Mochida S | Year | 2016 |
| Journal | Cell Rep | Volume | 16 |
| Issue | 11 | Pages | 2901-2913 |
| PubMed ID | 27626661 | Mgi Jnum | J:238996 |
| Mgi Id | MGI:5824758 | Doi | 10.1016/j.celrep.2016.08.020 |
| Citation | Mochida S, et al. (2016) SAD-B Phosphorylation of CAST Controls Active Zone Vesicle Recycling for Synaptic Depression. Cell Rep 16(11):2901-13 |
| abstractText | 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. |
