Neuropilin is a type I transmembrane protein and the molecular mass is 120 kDa. Two homologues, Neuropilin-1 and Neuropilin-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. Neuropilin-1 (NRP1) acts as a receptor for two different extracellular ligands, class 3 semaphorins and specific isoforms of vascular endothelial growth factor. The functions of NRP1 and NRP2 have been extensively studied in neurons where they act in axon guidance and in endothelial cells where they promote angiogenesis and cell migration. Neuropilin-1 is likely to mediate contacts between the dendritic cells and the T lymphocytes via homotypic interactions and is essential for the initiation of the primary immune response. NRP1 is a co-receptor for VEGF receptor-2 (VEGFR2) that enhances the binding of VEGF165 to VEGFR2 and VEGF165-mediated chemotaxis. NRP1 expression is regulated in EC by tumor necrosis factor-alpha, the transcription factors dHAND and Ets-1, and vascular injury. NRP1 upregulation is positively correlated with the progression of various tumors. Overexpression of NRPI in rat tumor cells results in enlarged tumors and substantially enhanced tumor angiogenesis. On the other hand, soluble NRP1 (sNRP1) is an antagonist of tumor angiogenesis.
Neuropilin-2 (NRP-2) which is related to NRP-1, is a type I transmembrane glycoprotein and has the structure characteristic with five main extracellular domains: two complement binding (CUB) domains, two coagulation factor V/VIII homology domains, and a MAM (meprin, tyrosine phosphatase domain) region. NRP-2 is a receptor capable of binding two disparate ligands, classⅢ semaphorins (SEMA) and vascular endothelial growth factors (VEGF), and thus regulates two diverse systems by activating cellular signaling pathways via interacting with other cell surface receptors such as VEGF receptors and plexins. NRP-2 is well known for its role in facilitating axonal guidance during the development of the neuronal system, and additionally, it is also expressed in vascular endothelial cells and lymphatic endothelium where it affects proliferation, migration, angiogenesis, as well as the formation of small lymphatic vessels and capillaries. A recent study has identified NRP-2 as a polysialylation protein expressed in human dendritic cells and modulates DC-T Cell Interactions. Nearly all tumor cells express neuropilins and NRP-2 is predominantly expressed in neuronal tumors and melanomas. Furthermore, it is suggested that as the specific ligand for NRP-2, SEMA 3F inhibits tumor angiogenesis, and metastasis.
Neuroplastin (NPTN) is a 52-57 kDa member of the Ig-superfamily. Neuroplastin likely serves as a cell adhesion molecule, and is widely expressed in multiple tissues. Human Neuroplastin is 282 amino acids that contions two Ig-like domains and a 38 aa cytoplasmic region. Probable homophilic and heterophilic cell adhesion molecule involved in long term potentiation at hippocampal excitatory synapses through activation of p38MAPK. Neuroplastin may also regulate neurite outgrowth by activating the FGFR1 signaling pathway. It may play a role in synaptic plasticity.
DPEP2 (MBD-2) belongs to the membrane-bound dipeptidase family. There are three members of this family as membrane-bound dipeptidase-1 (MBD-1),membrane-bound dipeptidase-2 (MBD-2) and membrane-bound dipeptidase-3 (MBD-3).MBD-2 is expressed at highest levels in lung, heart, and testis and at some what lower levels in spleen.MBD-2 is membrane-bound through a glycosylphosphatidyl-inositol linkage and probably is a metalloprotease which hydrolyzes leukotriene D4 (LTD4) into leukotriene E4 (LTE4).It is generally recognized that rapid cleavage of LTD4 is important in inactivating the broncho-and vaso-constrictive effects of cysteinyl LTs in asthmatic and inflammatory processes.
Neurotrimin is a glycoprotein. It belongs to the immunoglobulin superfamily and IgLON family. Neurotrimin localizes to the cell membrane and contains three Ig-like C2-type domains. Neurotrimin acts as a glycosylphosphatidylinositol (GPI)-anchored neural cell adhesion molecule. Neurotrimin may promote neurite outgrowth and adhesion via homophilic and heterophilic interactions.
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