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 (b1/62) 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. PlexinA 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.
KeywordsVascular Endothelial Growth Factor Carboxyl Terminus Vascular Endothelial Cell Growth Factor Porcine Aortic Endothelial Cell Growth Cone Collapse
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