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, mu) 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.
authors.affiliation: Department of Neurology, Yale University School of Medicine, New Haven, Connecticut 06510, USA.
authors.forename: F
authors.initials: F
authors.lastname: Nakamura
authors.forename: M
authors.initials: M
authors.lastname: Tanaka
authors.forename: T
authors.initials: T
authors.lastname: Takahashi
authors.forename: R G
authors.initials: RG
authors.lastname: Kalb
authors.forename: S M
authors.initials: SM
authors.lastname: Strittmatter
mesh_terms: D000818:Animals; D002460:Cell Line; D002478:Cells, Cultured; D002642:Chick Embryo; D005110:Extracellular Space / Q000502:physiology*; D006023:Glycoproteins / Q000235:genetics / Q000494:pharmacology*; D020439:Growth Cones / Q000502:physiology*; D006801:Humans; D051379:Mice; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000502:physiology*; D039942:Neuropilin-1; D010446:Peptide Fragments / Q000502:physiology; D011485:Protein Binding; D017434:Protein Structure, Tertiary; D012165:Retinal Ganglion Cells / Q000166:cytology; D040121:Semaphorin-3A
chemical_list: D006023:Glycoproteins; D009419:Nerve Tissue Proteins; D010446:Peptide Fragments; D040121:Semaphorin-3A; D039942:Neuropilin-1