Semaphorins with

Adams, R. H., Betz, H., and Piischel, A. W. (1996). A novel class of murine semaphorins with homology to thrombospondin is differentially expressed during early embryo-genesis. Mech. Dev. 57, 33-45. 

Neuropilin-1 (NRP1), a molecule that had been previously shown to be implicated in axon guidance as a receptor for members of collapsin/semaphorin family, has been characterized as a which interacts with the heparin-binding VEGF isoforms. 

Subsequent studies have identified Rndl (Oinuma et al, 2003), another member of the Rho GTPase subfamily, and the ErbB-2 tyrosine kinase (Swiercz et al, 2004) in the regulation of RhoA by plexins. Additionally, an apparent requirement for interaction of plexin B with RhoGEFs for potentiation of angiogenesis by semaphorins (Basile et al., 2004) and activation of MAPK pathways (Aurandt et al, 2006) by plexin Bl was identified. Yet, direct evidence for the mechanism by which plexins achieve this activation of RhoA has been elusive. A simple mechanism would be localization of the RhoGEF to membranes on stimulation of the pathway as discussed in Section III.B. Evidence for this comes from a study (Oinuma et al, 2003) with Rndl, which can bind directly to plexin Bl. 

Aurandt, J., Vikis, H. G., Gutkind, J. S., Ahn, N., and Guan, K. L. (2002). The semaphorin receptor plexin-Bl signals through a direct interaction with the Rho-specific nucleotide exchange factor, LARG. Proc. Natl. Acad. Sci. USA 99, 12085-12090. 

Vertebrate A-Plexins are the signaling subunits for secreted class 3 semaphorins, while other plexins interact with semaphorins from different classes (Fiore and Piischel, 2003). In contrast to SemaSA, which is not able to bind directly to A-Plexins, SemalD and Sema7A directly interact with Plexin-Bl and Plexin-Cl, respectively (Takahashi et al, 1999 Tamagnone et al, 1999). Interestingly, all Plexins contain an extracellular semaphorin domain that is strictly required for their function (Fig. 7). A semaphorin domain is also present in the scatter-factor receptor MET (Tamagnone et al, 1999). 

Fig. 9. Non-covalent semaphorin dimerization mediated by the sema domains. (A) The Sema3A-65K dimer in the asymmetric unit of the crystals. (B) The interacting sema domains in the Sema4D dimer viewed in the same orientation as in (A). The expansive dimerization interface (total buried area of approximately 3000 A ) is generated by the approximation of four protruding loops from each monomer. These loops, located at the top face of the fi propeller are also implicated in interactions with the semaphorin receptors.

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