A PDZ protein regulates the distribution of the transmembrane semaphorin, M-SemF

Li Hsien Wang, Robert G. Kalb, Stephen M. Strittmatter*, F. Nakamura, M. Tanaka

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

100 Scopus citations

Abstract

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 MSemF 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. Coexpression 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.

Original languageEnglish (US)
Pages (from-to)14137-14146
Number of pages10
JournalJournal of Biological Chemistry
Volume274
Issue number20
DOIs
StatePublished - May 14 1999

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology

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