Eckhardt F, Behar O, Calautti E, Yonezawa K, Nishimoto I, Fishman MC. 1997. A novel transmembrane semaphorin can bind c-src. Molecular and cellular neurosciences. 9(5-6):409-19. Pubmed: 9361278


The semaphorins/collapsins constitute a family of genes unified by the presence of a "semaphorin domain" which has been conserved through metazoan evolution. The semaphorin family comprises both secreted and transmembrane molecules and is thought to be made up of ligands for as yet unidentified receptors. The functions are not known, with the exception of those of sema III (also referred as sem D and collapsin 1), D-sema I, and D-sema II, which have been shown to be involved in axonal pathfinding. Here report the identification of a mouse semaphorin cDNA, termed Sema VIb. Although Sema VIb contains the extracellular semaphorin domain, it lacks the immunoglobulin domain or thrombospondin repeats which are present in other described vertebrate (but not invertebrate) transmembrane semaphorins. During development Sema VIb mRNA is expressed in subregions of the nervous system and is particularly prominent in muscle. In adulthood, Sema VIb mRNA is expressed ubiquitously. The cytoplasmic domain of Sema VIb contains several proline-rich potential SH3 domain binding sites. Using an in vitro binding assay, we show that Sema VIb binds specifically the SH3 domain of the protooncogene c-src. In transfected COS cells Sema VIb coimmunoprecipitates with c-src. These results, along with our evidence that Sema VIb can form dimers, suggests that the semaphorin family not only serves as ligands but may include members, especially those which are transmembrane, which serve as receptors, triggering intracellular signaling via an src-related cascade.

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Photo of Mark C. Fishman

Mark C. Fishman’s group studies the heart-brain connection. They employ a range of genetic, developmental, and neurobiological tools in zebrafish to understand what the heart tells the brain, and how critical internal sensory systems adjust homeostatic and somatic behaviors, including social interactions.

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