Structural and functional relation of neuropilins.
Neuropilin is a type I transmembrane protein and the molecular mass is 120 kDa. Two homologues, Neuropilin-1 and -2, are identified. The primary structure of Neuropilin-1 and Neuropilin-2 is well conserved and is divided into four domains, CUB (a1/a2) domain, FV/FVIII (b1/b2) domain, MAM (c) domain, and (d) domain that contains a transmembrane and a short cytoplasmic region. Both Neuropilin-1 and Neuropilin-2 have truncated and secreted form of splice variants. Neuropilins act as a receptor for two different extracellular ligands, class 3 semaphorins and specific isoforms of vascular endothelial growth factor. In both cases, neuropilin requires an additional transmembrane molecule to exhibit biological activity. Plexin-A is essential for class 3 semaphorin signaling. Vascular endothelial cell growth factor (VEGF) receptor is the major receptor for VEGF and neuropilin acts as isoform specific co-receptor for VEGF. The CUB and FV/FVIII domains of Neuropilin are the binding sites of semaphorin and VEGF. The MAM domain mediates semaphorin signaling to Plexin-A. Cross talk between semaphorin and VEGF on neuropilin suggests that class 3 semaphorins and the secreted forms of neuropilin act as antagonists to VEGF and its related growth factors.
Nakamura
Fumio
F
Department of Molecular Pharmacology and Neurobiology, Yokohama City University School of Medicine, 3-9 Fukuura, Kanazawa-ku, Yokohama, Kanagawa, 236-0004, Japan.
Goshima
Yoshio
Y
D000818:Animals; D006801:Humans; D039942:Neuropilin-1 / Q000737:chemistry / Q000378:metabolism; D039921:Neuropilins / Q000737:chemistry* / Q000235:genetics / Q000502:physiology*; D011485:Protein Binding; D015398:Signal Transduction / Q000502:physiology
D039921:Neuropilins; D039942:Neuropilin-1