Plexins are a family of large integral membrane proteins that complex with neuropilins to form semaphorin co-receptors. The extracellular region of plexins contain a semaphorin domain, multiple glycine rich motifs, and MET related sequences. The cytoplasmic region contains a Sex/Plexin domain and putative tyrosine phosphorylation sites that mediate signal transduction after activation. This region in Plexin A1 binds the RhoGTPases, Rnd1 and RhoD. Recruitment of Rnd1 has been implicated in the cytoskeletal collapse that occurs after semaphorin mediated activation of Plexin A1, while RhoD may block this collapsing activity through interaction with the cytoplasmic region of Plexin A1. The expression of Plexin A1, along with the co receptor Neuropilin 1, is upregulated in neurons after central nervous system injury. The axons from these neurons cannot cross semaphorin 3A containing regions at the site of injury. Thus, semaphorin 3A and its co-receptors, Plexin A1 and Neuropilin 1, may have significant roles in axon regeneration after neuronal injury.