Plexin-neuropilin-1 complexes form functional semaphorin-3A receptors.
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 affinity 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-negative 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 complexes.
Takahashi
T
T
Department of Neurology, Yale University School of Medicine, New Haven, Connecticut 06510, USA.
Fournier
A
A
Nakamura
F
F
Wang
L H
LH
Murakami
Y
Y
Kalb
R G
RG
Fujisawa
H
H
Strittmatter
S M
SM
D000818:Animals; D019556:COS Cells; D005727:Ganglia, Spinal / Q000166:cytology; D015870:Gene Expression / Q000502:physiology; D020439:Growth Cones / Q000737:chemistry / Q000378:metabolism; D006801:Humans; D007668:Kidney / Q000166:cytology; D005810:Multigene Family; D009419:Nerve Tissue Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D009474:Neurons / Q000737:chemistry / Q000166:cytology / Q000648:ultrastructure; D039942:Neuropilin-1; D011485:Protein Binding / Q000502:physiology; D017434:Protein Structure, Tertiary; D011956:Receptors, Cell Surface / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction / Q000502:physiology; D012995:Solubility; D014162:Transfection
D009419:Nerve Tissue Proteins; C492116:PLXNA1 protein, human; D011956:Receptors, Cell Surface; D039942:Neuropilin-1