| Class 3 secreted semaphorin (Sema3A) is a chemorepellent that acts upon a wide variety of axons. As such, it induces a dramatic redistribution and depolymerization of actin filaments that results in growth cone collapse. Plexins are single membrane-spanning signaling proteins encompassing Plexin A1, A2, A3, and A4. Plexins form a complex with neuropilin-1 and -2 and the cell adhesion protein L1 to form a functional semaphorin receptor. The GTPase Rnd1 binds to the cytoplasmic domain of Plexin A1 to trigger cytoskeletal collapse. In contrast, the GTPase RhoD blocks Rnd1-mediated Plexin A1 activation and repulsion of sympathetic axons by Sema3A. Both Plexin A3 and A4 mediate the responses to class 3 semaphorins in sensory and sympathetic neurons. In particular, Plexin A4 is responsible for signaling of Sema 3A via neuropilin-1, while Plexin A3 is responsible for signaling of Sema 3F via neuropilin-2. |
