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

ASJC Scopus subject areas

  • Neuroscience(all)

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