Neuropilin-2 is a receptor for semaphorin IV: Insight into the structural basis of receptor function and specificity

Roman J. Giger, Erica Rowe Urquhart, Susan K H Gillespie, Dorothy V. Levengood, David D. Ginty, Alex L Kolodkin

Research output: Contribution to journalArticle

Abstract

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.

Original languageEnglish (US)
Pages (from-to)1079-1092
Number of pages14
JournalNeuron
Volume21
Issue number5
DOIs
StatePublished - Nov 1998

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Neuropilin-2
Neuropilin-1
Semaphorins
Neuropilins
Blood Coagulation Factors
Vascular Endothelial Growth Factor A
Immunoglobulins
Ligands
Neurons
semaphorin IV
Population
Proteins

ASJC Scopus subject areas

  • Neuroscience(all)

Cite this

Neuropilin-2 is a receptor for semaphorin IV : Insight into the structural basis of receptor function and specificity. / Giger, Roman J.; Urquhart, Erica Rowe; Gillespie, Susan K H; Levengood, Dorothy V.; Ginty, David D.; Kolodkin, Alex L.

In: Neuron, Vol. 21, No. 5, 11.1998, p. 1079-1092.

Research output: Contribution to journalArticle

Giger, Roman J. ; Urquhart, Erica Rowe ; Gillespie, Susan K H ; Levengood, Dorothy V. ; Ginty, David D. ; Kolodkin, Alex L. / Neuropilin-2 is a receptor for semaphorin IV : Insight into the structural basis of receptor function and specificity. In: Neuron. 1998 ; Vol. 21, No. 5. pp. 1079-1092.
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