Neuropilin-2, a novel member of the neuropilin family, is a high affinity receptor for the semaphorins Sema E and Sema IV but not Sema III.
Semaphorins are a large family of secreted and transmembrane proteins, several of which are implicated in repulsive axon guidance. Neuropilin (neuropilin-1) was recently identified as a receptor for Collapsin-1/Semaphorin III/D (Sema III). We report the identification of a related protein, neuropilin-2, whose mRNA is expressed by developing neurons in a pattern largely, though not completely, nonoverlapping with that of neuropilin-1. Unlike neuropilin-1, which binds with high affinity to the three structurally related semaphorins Sema III, Sema E, and Sema IV, neuropilin-2 shows high affinity binding only to Sema E and Sema IV, not Sema III. These results identify neuropilins as a family of receptors (or components of receptors) for at least one semaphorin subfamily. They also suggest that the specificity of action of different members of this subfamily may be determined by the complement of neuropilins expressed by responsive cells.
Chen
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Howard Hughes Medical Institute, Department of Anatomy, University of California, San Francisco 94143-0452, USA.
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Goodman
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Tessier-Lavigne
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D000818:Animals; D002352:Carrier Proteins / Q000378:metabolism*; D002531:Cerebellum / Q000737:chemistry / Q000196:embryology; D005728:Ganglia, Sympathetic / Q000737:chemistry / Q000196:embryology; D018507:Gene Expression Regulation, Developmental / Q000502:physiology; D006023:Glycoproteins / Q000378:metabolism*; D006624:Hippocampus / Q000737:chemistry / Q000196:embryology; D051379:Mice; D008969:Molecular Sequence Data; D019579:Neocortex / Q000737:chemistry / Q000196:embryology; D009414:Nerve Growth Factors / Q000378:metabolism*; D009419:Nerve Tissue Proteins / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism*; D009474:Neurons / Q000737:chemistry / Q000502:physiology; D039942:Neuropilin-1; D009833:Olfactory Pathways / Q000737:chemistry / Q000196:embryology; D011485:Protein Binding / Q000502:physiology; D011956:Receptors, Cell Surface / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism; D012249:Rhombencephalon / Q000737:chemistry / Q000196:embryology; D040121:Semaphorin-3A; D017386:Sequence Homology, Amino Acid; D013116:Spinal Cord / Q000737:chemistry / Q000166:cytology / Q000196:embryology; D013788:Thalamus / Q000737:chemistry / Q000196:embryology; D014795:Visual Pathways / Q000737:chemistry / Q000196:embryology
D002352:Carrier Proteins; D006023:Glycoproteins; D009414:Nerve Growth Factors; D009419:Nerve Tissue Proteins; D011956:Receptors, Cell Surface; C488217:Sema3a protein, mouse; D040121:Semaphorin-3A; C099436:semaphorin IV; D039942:Neuropilin-1