Rickman Colin, Craxton Molly, Osborne Shona, Davletov Bazbek
MRC Laboratory of Molecular Biology, Hills Road, Cambridge CB2 2QH, UK.
Biochem J. 2004 Mar 1;378(Pt 2):681-6. doi: 10.1042/BJ20031407.
Intracellular membrane traffic is governed by a conserved set of proteins, including Syts (synaptotagmins). The mammalian Syt family includes 15 isoforms. Syts are membrane proteins that possess tandem C2 domains (C2AB) implicated in calcium-dependent phospholipid binding. We performed a pair-wise amino acid sequence comparison, together with functional studies of rat Syt C2ABs, to examine common and divergent properties within the mammalian family. Sequence analysis indicates three different C2AB classes, the members of which share a high degree of sequence similarity. All the other C2ABs are highly divergent in sequence. Nearly half of the Syt family does not exhibit calcium/phospholipid binding in comparison to Syt I, the major brain isoform. Syts do, however, possess a more conserved function, namely calcium-independent binding to target SNARE (soluble N-ethylmaleimide-sensitive fusion protein attachment protein receptor) heterodimers. All tested isoforms, except Syt XII and Syt XIII, bound the target SNARE heterodimer comprising syntaxin 1 and SNAP-25 (25 kDa synaptosome-associated protein). Our present study suggests that many Syt isoforms can function in membrane trafficking to interact with the target SNARE heterodimer on the pathway to calcium-triggered membrane fusion.
细胞内膜运输由一组保守的蛋白质控制，包括突触结合蛋白（Syts）。哺乳动物的突触结合蛋白家族包括15种亚型。突触结合蛋白是膜蛋白，具有串联C2结构域（C2AB），与钙依赖性磷脂结合有关。我们进行了成对氨基酸序列比较，并对大鼠突触结合蛋白C2AB进行了功能研究，以研究哺乳动物家族中的共同和不同特性。序列分析表明存在三种不同的C2AB类别，其成员具有高度的序列相似性。所有其他C2AB在序列上高度不同。与主要的脑亚型突触结合蛋白I相比，近一半的突触结合蛋白家族不表现出钙/磷脂结合。然而，突触结合蛋白确实具有一种更保守的功能，即与靶标SNARE（可溶性N-乙基马来酰亚胺敏感融合蛋白附着蛋白受体）异二聚体的钙非依赖性结合。除了突触结合蛋白XII和突触结合蛋白XIII外，所有测试的亚型都与由 syntaxin 1和SNAP-25（25 kDa突触体相关蛋白）组成的靶标SNARE异二聚体结合。我们目前的研究表明，许多突触结合蛋白亚型可以在膜运输中发挥作用，在钙触发的膜融合途径中与靶标SNARE异二聚体相互作用。
