Although neuropilin-1 is required for Sema-3A action, it is incapable of transmitting a Sema-3A signal to the growth cone interior. The function of Sema-3A is mediated by Plexins. Sema-3A binds with high affinity to Plexin when the latter is complexed with Neuropilin-1. Plexin-A1 is known to act as an R-Ras GAP (GTPase activating protein) when bound by Sema-3A. Plexin's GAP activity is regulated by FARP2 mediated Rac1 activation. Sema-3A binding to neuropilin-1/Plexin-A1 seems to induce a conformational change of plexin-A1 necessary for releasing FARP2. This suggests that neuropilin1 is required not only for ligand binding, but also for signaling, by modulating the interaction of FARP2 with plexin-A1.
Zhang, H, Yoshida, J, Toyofuku, T, Kumanogoh, A, Sugimoto, T, Kikutani, H, Hori, M
Raper, JA
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