Fukuda M, Mikoshiba K
Laboratory for Developmental Neurobiology, Brain Science Institute, RIKEN, 2-1 Hirosawa, Wako, Saitama, 351-0198, Japan.
Biochem Biophys Res Commun. 2001 Mar;281(5):1226-33. doi: 10.1006/bbrc.2001.4512.
Synaptotagmins (Syt), rabphilin-3A, and Doc2 belong to a family of carboxyl terminal type (C-type) tandem C2 proteins and are thought to be involved in vesicular trafficking. We have cloned and characterized a novel family of C-type tandem C2 proteins, designated Slp1-3 (synaptotagmin-like protein 1-3). The Slp1-3 C2 domains show high homology to granuphilin-a C2 domains, but the amino-terminal domain of Slp1-3 does not contain any known protein motifs or a transmembrane domain. A subcellular fractionation study indicated that Slp1-3 proteins are peripheral membrane proteins. Phospholipid binding experiments indicated that Slp3 is a Ca(2+)-dependent isoform, but Slp1 and Slp2 are Ca(2+)-independent isoforms, because only the Slp3 C2A domain showed Ca(2+)-dependent phospholipid binding activity. The C-terminus of Slp1-3 also bound neurexin Ialpha in vitro, in the same manner as Syt family proteins, which may be important for the membrane association of Slp1-3. In addition, Slp family proteins are differentially distributed in different mouse tissues and at different developmental stages.
突触结合蛋白（Syt）、rabphilin-3A和Doc2属于羧基末端型（C型）串联C2蛋白家族，被认为参与囊泡运输。我们克隆并鉴定了一个新的C型串联C2蛋白家族，命名为Slp1-3（突触结合蛋白样蛋白1-3）。Slp1-3的C2结构域与嗜铬粒蛋白-a的C2结构域具有高度同源性，但Slp1-3的氨基末端结构域不包含任何已知的蛋白质基序或跨膜结构域。亚细胞分级分离研究表明，Slp1-3蛋白是外周膜蛋白。磷脂结合实验表明，Slp3是一种钙依赖型异构体，但Slp1和Slp2是钙非依赖型异构体，因为只有Slp3的C2A结构域显示出钙依赖型磷脂结合活性。Slp1-3的C末端在体外也与神经连接蛋白Iα结合，方式与Syt家族蛋白相同，这可能对Slp1-3的膜结合很重要。此外，Slp家族蛋白在不同的小鼠组织和不同的发育阶段有不同的分布。
