TY - JOUR
T1 - Neuropilin-1 extracellular domains mediate semaphorin D/III-induced growth cone collapse
AU - Nakamura, Fumio
AU - Tanaka, Masaki
AU - Takahashi, Takuya
AU - Kalb, Robert G.
AU - Strittmatter, Stephen M.
N1 - Funding Information:
The authors thank Eisaku Kondo (Okayama, Japan) for advice on silane-treated fixation, Alyson Fournier (S. M. S. Laboratory) for advice on retinal explant preparation, Hajime Fujisawa (Nagoya, Japan) for providing anti-Npn-1 antibody, Junich Miyazaki (Sendai, Japan) for providing pCAG vector, Alex L. Kolodkin (Baltimore, Maryland) for a gift of rat NP2a cDNA, and Marc Tessier-Lavigne (San Francisco, California) for providing various mouse NP2 isoform cDNAs. This work was supported by a grant to F. N. and S. M. S. from the Spinal Cord Research Fund of the Paralyzed Veterans of America and by a grant to S. M. S. from the National Institutes of Health. S. M. S. is a John Merck Scholar in the Biology of Developmental Disorders in Children.
PY - 1998/11
Y1 - 1998/11
N2 - Somatosensory axon outgrowth is repulsed when soluble semaphorin D (semD) binds to growth cone neuropilin-1 (Npn-1). Here, semD ligand binding studies of Npn-1 mutants demonstrate that the sema domain binds to the amino- terminal quarter, or complement-binding (CUB) domain, of Npn-1. By herpes simplex virus- (HSV-) mediated expression of Npn-1 mutants in chick retinal ganglion cells, we show that semD-induced growth cone collapse requires two segments of the ectodomain of Npn-1, the CUB domain and the juxtamembrane portion, or MAM (meprin, A5, μ) domain. In contrast, the transmembrane segment and cytoplasmic tail of Npn-1 are not required for biologic activity. These data imply that the CUB and MAM ectodomains of Npn-1 interact with another transmembrane growth cone protein that in turn transduces a semD signal into axon repulsion.
AB - Somatosensory axon outgrowth is repulsed when soluble semaphorin D (semD) binds to growth cone neuropilin-1 (Npn-1). Here, semD ligand binding studies of Npn-1 mutants demonstrate that the sema domain binds to the amino- terminal quarter, or complement-binding (CUB) domain, of Npn-1. By herpes simplex virus- (HSV-) mediated expression of Npn-1 mutants in chick retinal ganglion cells, we show that semD-induced growth cone collapse requires two segments of the ectodomain of Npn-1, the CUB domain and the juxtamembrane portion, or MAM (meprin, A5, μ) domain. In contrast, the transmembrane segment and cytoplasmic tail of Npn-1 are not required for biologic activity. These data imply that the CUB and MAM ectodomains of Npn-1 interact with another transmembrane growth cone protein that in turn transduces a semD signal into axon repulsion.
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U2 - 10.1016/S0896-6273(00)80626-1
DO - 10.1016/S0896-6273(00)80626-1
M3 - Article
C2 - 9856464
AN - SCOPUS:0032215735
SN - 0896-6273
VL - 21
SP - 1093
EP - 1100
JO - Neuron
JF - Neuron
IS - 5
ER -