title: Neuropilin-2 is a receptor for semaphorin IV: insight into the structural basis of receptor function and specificity.
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- (Ig-) 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.
authors.affiliation: Department of Neuroscience, The Johns Hopkins University School of Medicine, Baltimore, Maryland 21205-2185, USA.
authors.forename: R J
authors.initials: RJ
authors.lastname: Giger
authors.forename: E R
authors.initials: ER
authors.lastname: Urquhart
authors.forename: S K
authors.initials: SK
authors.lastname: Gillespie
authors.forename: D V
authors.initials: DV
authors.lastname: Levengood
authors.forename: D D
authors.initials: DD
authors.lastname: Ginty
authors.forename: A L
authors.initials: AL
authors.lastname: Kolodkin
mesh_terms: D000818:Animals; D002478:Cells, Cultured; D018920:Coculture Techniques; D004622:Embryo, Mammalian; D005727:Ganglia, Spinal / Q000166:cytology; D005728:Ganglia, Sympathetic / Q000166:cytology; D006023:Glycoproteins / Q000502:physiology; D006801:Humans; D009414:Nerve Growth Factors / Q000378:metabolism* / Q000502:physiology; D009419:Nerve Tissue Proteins / Q000096:biosynthesis / Q000378:metabolism* / Q000502:physiology; D009474:Neurons / Q000378:metabolism; D039942:Neuropilin-1; D051381:Rats; D011956:Receptors, Cell Surface / Q000737:chemistry / Q000502:physiology*; D040121:Semaphorin-3A; D017783:Superior Cervical Ganglion / Q000737:chemistry / Q000166:cytology
chemical_list: D006023:Glycoproteins; D009414:Nerve Growth Factors; D009419:Nerve Tissue Proteins; D011956:Receptors, Cell Surface; D040121:Semaphorin-3A; C099436:semaphorin IV; D039942:Neuropilin-1