Class 1 and 3 semaphorins repulse axons but bind to different cell surface
proteins. We find that the two known semaphorin-binding proteins, plexin 1
(Plex 1) and neuropilin-1 (NP-1), form a stable complex. Plex 1 alone does
not bind semaphorin-3A (Sema3A), but the NP-1/Plex 1 complex has a higher a
ffinity for Sema3A than does NP-1 alone. While Sema3A binding to NP-1 does
not alter nonneuronal cell morphology, Sema3A interaction with NP-1/Plex 1
complexes induces adherent cells to round up. Expression of a dominant-nega
tive Plex 1 in sensory neurons blocks Sema3A-induced growth cone collapse.
Sema3A treatment leads to the redistribution of growth cone NP-1 and plexin
into clusters. Thus, physiologic Sema3A receptors consist of NP-1/plexin c
omplexes.