III semaphorins

To date, six members of class III semaphorins (Sema-3A to Sema-3F) have been identified, and these members have been reported by a number of studies to function as chemorepellents to distinct sets of axons (reviewed in [45]). Furthermore, there are studies demonstrating that some members of class III semaphorins can act as chemoattractants as well as chemorepellents. 

The receptor for class III semaphorins was identified independently by two groups [20, 29]. They screened a plasmid library by probing 

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Chen, H., He, Z., Bagii, A., and Tessier-Lavigne, M., Semaphorin—neuropilin interactions underlying sympathetic axon responses to class III semaphorins. Neuron, 21,1283,1998. 

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. 

Messersmith, E. K., Leonardo, E. D., Shatz, C. J., Tessier-Lavigne, M., Goodman, C. S., and Kolodkin, A. L. (1995). Semaphorin III can function as a selective chemo-repellent to pattern sensory projections in the spinal cord. Neuron 14, 949-959. 

Nakamura, F., Tanaka, M., Takahashi, T., Kalb, R. G., and Strittmatter, S. M. (1998). Neuropilin-1 extracellular domains mediate semaphorin D/III-induced growth cone collapse. Neuron 21, 1093-1100. 

Monoclonal antibody screens on grasshopper embryos uncovered a protein which, like Fasciclin I, II and III, is expressed on subsets of axons in the embryonic CNS. It was originally christened Fasciclin IV, but has more recently been renamed Semaphorin, as it has become clear that it differs in a number of fundamental respects from the Fas-ciclins (Kolodkin et al., 1992). The semaphorins are discussed in Section 5.2.1. 

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