TY - JOUR
T1 - Neuropilin-2 is a receptor for semaphorin IV
T2 - Insight into the structural basis of receptor function and specificity
AU - Giger, Roman J.
AU - Urquhart, Erica Rowe
AU - Gillespie, Susan K.H.
AU - Levengood, Dorothy V.
AU - Ginty, David D.
AU - Kolodkin, Alex L.
N1 - Funding Information:
D. D. G. and A. L. K. are senior coauthors. We thank B. Lee for technical assistance, D. Kantor for work on the neuropilin-2-expression experiments, D. Lo and A. Riccio for advice with particle-mediated gene transfer, M. Tessier-Lavigne for the AP-Sema IV and neuropilin-2(b) clones, P. Sonderegger for the axonin-1 clone, F. Polleux for help with imaging transfected neurons and with figures, Mark Molliver for critical reading of the manuscript, and members of the Ginty and Kolodkin laboratories for helpful discussions. This work was supported by a National Institutes of Health/National Institute of Mental Health grant (R01MH59199) (D. D. G. and A. L. K.), by National Institutes of Health National Research Service Award fellowships (E. U. and S. G.), and by the Schweizerischen Nationalfonds (R. G.).
PY - 1998/11
Y1 - 1998/11
N2 - Neuropilins bind secreted members of the semaphorin family of proteins. Neuropilin-1 is a receptor for Sema III. Here, we show that neuropilin-2 is a receptor for the secreted semaphorin Sema IV and acts selectively to mediate repulsive guidance events in discrete populations of neurons, neuropilin-2 and semaIV are expressed in strikingly complementary patterns during neurodevelopment. The extracellular complement-binding (CUB) and coagulation factor domains of neuropilin-2 confer specificity to the Sema IV repulsive response, and these domains of neuropilin-1 are necessary and sufficient for binding of the Sema III semaphorin (sema) domain. The coagulation factor domains alone are necessary and sufficient for binding of the Sema III immunoglobulin- (lg-) basic domain and the unrelated ligand, vascular endothelial growth factor (VEGF). Lastly, neuropilin-1 can homomultimerize and form heteromultimers with neuropilin-2. These results provide insight into how interactions between neuropilins and secreted semaphorins function to coordinate repulsive axon guidance during neurodevelopment.
AB - Neuropilins bind secreted members of the semaphorin family of proteins. Neuropilin-1 is a receptor for Sema III. Here, we show that neuropilin-2 is a receptor for the secreted semaphorin Sema IV and acts selectively to mediate repulsive guidance events in discrete populations of neurons, neuropilin-2 and semaIV are expressed in strikingly complementary patterns during neurodevelopment. The extracellular complement-binding (CUB) and coagulation factor domains of neuropilin-2 confer specificity to the Sema IV repulsive response, and these domains of neuropilin-1 are necessary and sufficient for binding of the Sema III semaphorin (sema) domain. The coagulation factor domains alone are necessary and sufficient for binding of the Sema III immunoglobulin- (lg-) basic domain and the unrelated ligand, vascular endothelial growth factor (VEGF). Lastly, neuropilin-1 can homomultimerize and form heteromultimers with neuropilin-2. These results provide insight into how interactions between neuropilins and secreted semaphorins function to coordinate repulsive axon guidance during neurodevelopment.
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U2 - 10.1016/S0896-6273(00)80625-X
DO - 10.1016/S0896-6273(00)80625-X
M3 - Article
C2 - 9856463
AN - SCOPUS:0032215144
SN - 0896-6273
VL - 21
SP - 1079
EP - 1092
JO - Neuron
JF - Neuron
IS - 5
ER -