Protein receptor active in neurons
Protein family
Neuropilin is aprotein receptor active inneurons .
There are two forms of Neuropilins,NRP-1 andNRP-2 . Neuropilins are transmembraneglycoproteins , first documented to regulateneurogenesis andangiogenesis by complexing withPlexin receptors/class-3semaphorin ligands andVascular Endothelial Growth Factor (VEGF) receptors/VEGF ligands, respectively.[ 2] [ 3] cytoplasmic domain and thus rely upon other cell surface receptors to transduce their signals across acell membrane .[ 2] [ 3] Epidermal Growth Factor (EGF),Fibroblast Growth Factor (FGF),Hepatocyte Growth Factor (HGF),Insulin-like Growth Factor (IGF),Platelet Derived Growth Factor (PDGF) andTransforming Growth Factor beta (TGFβ).[ 4] [ 5] [ 6] [ 7] alternative splicing or byectodomain shedding from the cell surface.[ 8] [ 9]
Thepleiotropic nature of the NRP receptors results in their involvement in cellular processes, such asaxon guidance andangiogenesis , theimmune response andremyelination .[ 10] cancer andcardiovascular disease .[ 11] [ 12] [ 13] [ 14]
Neuropilin-1 is a therapeutic target protein in the treatment forleukemia andlymphoma , since It has been shown that there is increased expression in neuropilin-1 in leukemia and lymphoma cell lines.[ 15] antagonism of neuropilin-1 has been found to inhibit tumourcell migration andadhesion .[ 16]
Neuropilins contain the following four domains:
The structure of B1 domain (coagulation factor 5/8 type) of neuropilin-1 was determined through X-Ray Diffraction with a resolution of 2.90 Å. The secondary structure of this domain is 5%alpha helical and 46%beta sheet .[ 1]
^a b PDB :3I97 Jarvis A, Allerston CK, Jia H, Herzog B, Garza-Garcia A, Winfield N, et al. (March 2010)."Small molecule inhibitors of the neuropilin-1 vascular endothelial growth factor A (VEGF-A) interaction" .Journal of Medicinal Chemistry .53 (5):2215– 26.doi :10.1021/jm901755g .PMC 2841442 PMID 20151671 . ^a b Pellet-Many C, Frankel P, Jia H, Zachary I (April 2008). "Neuropilins: structure, function and role in disease".The Biochemical Journal .411 (2):211– 26.doi :10.1042/bj20071639 .PMID 18363553 . ^a b Schwarz Q, Ruhrberg C (January 2010)."Neuropilin, you gotta let me know: should I stay or should I go?" .Cell Adhesion & Migration .4 (1):61– 6.doi :10.4161/cam.4.1.10207 .PMC 2852559 PMID 20026901 . ^ Kofler N, Simons M (May 2016)."The expanding role of neuropilin: regulation of transforming growth factor-β and platelet-derived growth factor signaling in the vasculature" .Current Opinion in Hematology .23 (3):260– 7.doi :10.1097/moh.0000000000000233 .PMC 4957701 PMID 26849476 . ^ Roy S, Pramanik A, Chakraborti T, Chakraborti S (2017). "Multifaceted Role of Matrix Metalloproteases on Human Diseases".Proteases in Human Diseases . Springer Singapore. pp. 21– 40.doi :10.1007/978-981-10-3162-5_2 .ISBN 978-981-10-3161-8 ^ Issitt T, Bosseboeuf E, De Winter N, Dufton N, Gestri G, Senatore V, et al. (January 2019)."Neuropilin-1 Controls Endothelial Homeostasis by Regulating Mitochondrial Function and Iron-Dependent Oxidative Stress" .iScience .11 :205– 223.Bibcode :2019iSci...11..205I .doi :10.1016/j.isci.2018.12.005 .PMC 6327076 PMID 30623799 . ^ Mehta V, Fields L, Evans IM, Yamaji M, Pellet-Many C, Jones T, et al. (August 2018)."VEGF (Vascular Endothelial Growth Factor) Induces NRP1 (Neuropilin-1) Cleavage via ADAMs (a Disintegrin and Metalloproteinase) 9 and 10 to Generate Novel Carboxy-Terminal NRP1 Fragments That Regulate Angiogenic Signaling" .Arteriosclerosis, Thrombosis, and Vascular Biology .38 (8):1845– 1858.doi :10.1161/ATVBAHA.118.311118 .PMC 6092111 PMID 29880492 . ^ Rossignol M, Gagnon ML, Klagsbrun M (December 2000). "Genomic organization of human neuropilin-1 and neuropilin-2 genes: identification and distribution of splice variants and soluble isoforms".Genomics .70 (2):211– 22.doi :10.1006/geno.2000.6381 .PMID 11112349 . ^ Werneburg S, Buettner FF, Erben L, Mathews M, Neumann H, Mühlenhoff M, et al. (August 2016). "Polysialylation and lipopolysaccharide-induced shedding of E-selectin ligand-1 and neuropilin-2 by microglia and THP-1 macrophages".Glia .64 (8):1314– 30.doi :10.1002/glia.23004 .PMID 27159043 .S2CID 3713077 . ^ Mecollari V, Nieuwenhuis B, Verhaagen J (2014)."A perspective on the role of class III semaphorin signaling in central nervous system trauma" .Frontiers in Cellular Neuroscience .8 : 328.doi :10.3389/fncel.2014.00328 PMC 4209881 PMID 25386118 . ^ Niland S, Eble JA (February 2019)."Neuropilins in the Context of Tumor Vasculature" .International Journal of Molecular Sciences .20 (3): 639.doi :10.3390/ijms20030639 PMC 6387129 PMID 30717262 . ^ Kofler N, Simons M (May 2016)."The expanding role of neuropilin: regulation of transforming growth factor-β and platelet-derived growth factor signaling in the vasculature" .Current Opinion in Hematology .23 (3):260– 7.doi :10.1097/MOH.0000000000000233 .PMC 4957701 PMID 26849476 . ^ Pellet-Many C, Mehta V, Fields L, Mahmoud M, Lowe V, Evans I, et al. (November 2015)."Neuropilins 1 and 2 mediate neointimal hyperplasia and re-endothelialization following arterial injury" .Cardiovascular Research .108 (2). Oxford University Press:288– 98.doi :10.1093/cvr/cvv229 .OCLC 927518632 .PMC 4614691 PMID 26410366 . ^ Harman JL, Sayers J, Chapman C, Pellet-Many C (2020-07-21)."Emerging Roles for Neuropilin-2 in Cardiovascular Disease" .International Journal of Molecular Sciences .21 (14): 5154.doi :10.3390/ijms21145154 PMC 7404143 PMID 32708258 . ^ Karjalainen K, Jaalouk DE, Bueso-Ramos CE, Zurita AJ, Kuniyasu A, Eckhardt BL, et al. (January 2011)."Targeting neuropilin-1 in human leukemia and lymphoma" .Blood .117 (3):920– 7.doi :10.1182/blood-2010-05-282921 .PMC 3298438 PMID 21063027 . ^ Jia H, Cheng L, Tickner M, Bagherzadeh A, Selwood D, Zachary I (February 2010)."Neuropilin-1 antagonism in human carcinoma cells inhibits migration and enhances chemosensitivity" .British Journal of Cancer .102 (3):541– 52.doi :10.1038/sj.bjc.6605539 .PMC 2822953 PMID 20087344 .
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