Different states of synaptotagmin regulate evoked versus spontaneous release

作者：Bai Hua; Xue Renhao; Bao Huan; Zhang Leili; Yethiraj Arun; Cui Qiang; Chapman Edwin R^*

来源：Nature Communications, 2016, 7(1): 10971.

DOI：10.1038/ncomms10971

The tandem C2-domains of synaptotagmin 1 (syt) function as Ca2+-binding modules that trigger exocytosis; in the absence of Ca2+, syt inhibits spontaneous release. Here, we used proline linkers to constrain and alter the relative orientation of these C2-domains. Short poly-proline helices have a period of three, so large changes in the relative disposition of the C2-domains result from changing the length of the poly-proline linker by a single residue. The length of the linker was varied one residue at a time, revealing a periodicity of three for the ability of the linker mutants to interact with anionic phospholipids and drive evoked synaptic transmission; syt efficiently drove exocytosis when its tandem C2-domains pointed in the same direction. Analysis of spontaneous release revealed a reciprocal relationship between the activation and clamping activities of the linker mutants. Hence, different structural states of syt underlie the control of distinct forms of synaptic transmission.

• 出版日期2016-3