Wang L H, Kalb R G, Strittmatter S M
Department of Neurology, Yale University School of Medicine, New Haven, Connecticut 06520, USA.
J Biol Chem. 1999 May 14;274(20):14137-46. doi: 10.1074/jbc.274.20.14137.
M-SemF is a membrane-associated, neurally enriched member of the semaphorin family of axon guidance signals. We considered whether the cytoplasmic domain of M-SemF might possess a signaling function and/or might control the distribution of M-SemF on the cell surface. We identify a PDZ-containing neural protein as an M-SemF cytoplasmic domain-associated protein (SEMCAP-1). SEMCAP-2 is a closely related nonneuronal protein. SEMCAP-1 has recently also been identified as GIPC, by virtue of its interaction with the RGS protein GAIP in vitro (De Vries, L., Lou, X., Zhao, G., Zheng, B., and Farquhar, M. G. (1998) Proc. Natl. Acad. Sci. U. S. A. 95, 12340-12345). Expression studies support the notion that SEMCAP-1(GIPC) interacts with M-SemF, but not GAIP, in brain. Lung SEMCAP-2 and SEMCAP-1(GIPC) are potential partners for both GAIP and M-SemF. The protein interaction requires the single PDZ domain of SEMCAP-1(GIPC) and the carboxyl-terminal four residues of M-SemF, ESSV. While SEMCAP-1(GIPC) also interacts with SemC, it does not interact with other proteins containing a class I PDZ binding motif, nor does M-SemF interact with other class I PDZ proteins. Co-expression of SEMCAP-1(GIPC) induces the redistribution of dispersed M-SemF into detergent-resistant aggregates in HEK293 cells. Thus, SEMCAP-1(GIPC) appears to regulate the subcellular distribution of M-SemF in brain, and SEMCAPs could link M-SemF to G protein signal transduction pathways.
M-SemF是轴突导向信号的信号素家族中一种与膜相关且在神经中高度富集的成员。我们思考了M-SemF的细胞质结构域是否可能具有信号传导功能和/或是否可能控制M-SemF在细胞表面的分布。我们鉴定出一种含PDZ结构域的神经蛋白作为与M-SemF细胞质结构域相关的蛋白（SEMCAP-1）。SEMCAP-2是一种密切相关的非神经蛋白。最近，SEMCAP-1也因其在体外与RGS蛋白GAIP的相互作用而被鉴定为GIPC（德弗里斯，L.，娄，X.，赵，G.，郑，B.，和法夸尔，M.G.（1998年）美国国家科学院院刊95，12340 - 12345）。表达研究支持了SEMCAP-1（GIPC）在脑中与M-SemF相互作用而非与GAIP相互作用的观点。肺中的SEMCAP-2和SEMCAP-1（GIPC）是GAIP和M-SemF的潜在伙伴。这种蛋白质相互作用需要SEMCAP-1（GIPC）的单个PDZ结构域和M-SemF的羧基末端四个残基ESSV。虽然SEMCAP-1（GIPC）也与SemC相互作用，但它不与其他含有I类PDZ结合基序的蛋白质相互作用，M-SemF也不与其他I类PDZ蛋白相互作用。SEMCAP-1（GIPC）的共表达诱导分散的M-SemF在HEK293细胞中重新分布形成耐去污剂的聚集体。因此，SEMCAP-1（GIPC）似乎在脑中调节M-SemF的亚细胞分布，并且SEMCAPs可能将M-SemF与G蛋白信号转导途径联系起来。
