Key Laboratory of Protein Chemistry and Developmental Biology of Ministry of Education, College of Life Sciences, Hunan Normal University, Changsha 410081, PR China; Institute of Bast Fiber Crops, Chinese Academy of Agricultural Sciences, Changsha 410205, PR China.
Key Laboratory of Protein Chemistry and Developmental Biology of Ministry of Education, College of Life Sciences, Hunan Normal University, Changsha 410081, PR China.
Biochem Biophys Res Commun. 2014 Feb 21;444(4):491-5. doi: 10.1016/j.bbrc.2014.01.090. Epub 2014 Jan 25.
Rab3 and synaptotagmin have been reported to be the key proteins that have opposite actions but cooperatively play critical regulatory roles in selecting and limiting the number of vesicles released at central synapses. However, the exact mechanism has not been fully understood. In this study, Rab3A and synaptotagmin I, the most abundant isoforms of Rab3 and synaptotagmin, respectively, in brain were for the first time demonstrated to directly interact with each other in a Ca(2+)-independent manner, and the KKKK motif in the C2B domain of synaptotagmin I was a key site for the Rab3A binding, which was further confirmed by the competitive inhibition of inositol hexakisphosphate. Further studies demonstrated that Rab3A competitively affected the synaptotagmin I interaction with syntaxin 1B that was involved in membrane fusion during the synaptic vesicle exocytosis. These data indicate that Rab3A is a new synaptotagmin I interacting partner and may participate in the regulation of synaptic membrane fusion and thus the vesicle exocytosis by competitively modulating the interaction of synaptotagmin with syntaxin of the t-SNARE complex in presynaptic membranes.
Rab3 和突触融合蛋白已被报道为在中枢突触中发挥关键调节作用的关键蛋白，它们具有相反的作用，但协同作用来选择和限制释放的囊泡数量。然而，其确切的机制尚未完全理解。在这项研究中，Rab3A 和突触融合蛋白 I（脑内 Rab3 和突触融合蛋白的最丰富同工型）首次被证明以 Ca2+ 非依赖性的方式直接相互作用，并且突触融合蛋白 I 的 C2B 结构域中的 KKKK 基序是 Rab3A 结合的关键位点，六磷酸肌醇的竞争抑制作用进一步证实了这一点。进一步的研究表明，Rab3A 竞争性地影响突触融合蛋白 I 与参与突触囊泡胞吐过程中膜融合的突触融合蛋白 1B 的相互作用。这些数据表明 Rab3A 是突触融合蛋白 I 的一个新的相互作用伙伴，可能通过竞争性调节突触融合蛋白与突触前膜中 t-SNARE 复合物的突触融合蛋白的相互作用，参与突触膜融合和囊泡胞吐的调节。
