Neuropilin-1 extracellular domains mediate semaphorin D/III-induced growth cone collapse

Fumio Nakamura; Masaki Tanaka; Takuya Takahashi; Robert G. Kalb; Stephen M. Strittmatter

doi:10.1016/S0896-6273(00)80626-1

Neuropilin-1 extracellular domains mediate semaphorin D/III-induced growth cone collapse

Fumio Nakamura, Masaki Tanaka, Takuya Takahashi, Robert G. Kalb, Stephen M. Strittmatter^*

^*Corresponding author for this work

Neurology

Research output: Contribution to journal › Article › peer-review

247 Scopus citations

Abstract

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.

Original language	English (US)
Pages (from-to)	1093-1100
Number of pages	8
Journal	Neuron
Volume	21
Issue number	5
DOIs	https://doi.org/10.1016/S0896-6273(00)80626-1
State	Published - Nov 1998

Funding

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.

ASJC Scopus subject areas

General Neuroscience

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10.1016/S0896-6273(00)80626-1

Cite this

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title = "Neuropilin-1 extracellular domains mediate semaphorin D/III-induced growth cone collapse",

abstract = "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.",

author = "Fumio Nakamura and Masaki Tanaka and Takuya Takahashi and Kalb, {Robert G.} and Strittmatter, {Stephen M.}",

note = "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.",

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AU - Strittmatter, Stephen M.

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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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Neuropilin-1 extracellular domains mediate semaphorin D/III-induced growth cone collapse

Abstract

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