Queensland Brain Institute, Clem Jones Centre for Ageing Dementia Research (CJCADR), The University of Queensland, Brisbane, QLD 4072, Australia.
Department of Biological Sciences, University of Illinois at Chicago, Chicago, IL 60607, USA.
Cell Rep. 2021 Mar 9;34(10):108828. doi: 10.1016/j.celrep.2021.108828.
Synapses exhibit multiple forms of short-term plasticities, which have been attributed to the heterogeneity of neurotransmitter release probability. However, the molecular mechanisms that underlie the differential release states remain to be fully elucidated. The Unc-13 proteins appear to have key roles in synaptic function through multiple regulatory domains. Here, we report that deleting the M domain in Caenorhabditis elegans UNC-13MR leads to a significant increase in release probability, revealing an inhibitory function of this domain. The inhibitory effect of this domain is eliminated when the C1 and C2B domains are absent or activated, suggesting that the M domain inhibits release probability by suppressing the activity of C1 and C2B domains. When fused directly to the MUNC2C fragment of UNC-13, the M domain greatly enhances release probability. Thus, our findings reveal a mechanism by which the UNC-13 M domain regulates synaptic transmission and provides molecular insights into the regulation of release probability.
突触表现出多种形式的短期可塑性，这归因于神经递质释放概率的异质性。然而，基础的分子机制仍有待充分阐明。Unc-13 蛋白似乎通过多个调节域在突触功能中发挥关键作用。在这里，我们报告说，在秀丽隐杆线虫 UNC-13MR 中删除 M 结构域会导致释放概率显著增加，揭示了该结构域的抑制功能。当 C1 和 C2B 结构域缺失或被激活时，该结构域的抑制作用会被消除，这表明 M 结构域通过抑制 C1 和 C2B 结构域的活性来抑制释放概率。当直接融合到 UNC-13 的 MUNC2C 片段时，M 结构域极大地增强了释放概率。因此，我们的发现揭示了 UNC-13 M 结构域调节突触传递的机制，并为释放概率的调节提供了分子见解。
