Neuropilin 2 Explained

Neuropilin 2 (NRP2) is a protein that in humans is encoded by the NRP2 gene.^{[1] [2]}

This gene encodes a member of the neuropilin family of receptor proteins. NRP2 is expressed by a wide variety of cell types. The transmembrane protein has been reported to bind to SEMA3C, SEMA3F, VEGF-A, VEGF-C, VEGF-D, TGFβ, integrins and ANGPTL4 to promote downstream signaling pathways. Consequently, NRP2 is known to play a role in cardiovascular development, axon guidance, tumorigenesis, inflammation and cardiovascular disease.^{[3] [4] [5] [6]} Multiple transcript variants encoding distinct isoforms have been identified for this gene.^[7]

Further reading

• Neufeld G, Cohen T, Gengrinovitch S, Poltorak Z . Vascular endothelial growth factor (VEGF) and its receptors . FASEB Journal . 13 . 1 . 9–22 . January 1999 . 9872925 . 10.1096/fasebj.13.1.9. free . 1151216 .
• Kolodkin AL, Levengood DV, Rowe EG, Tai YT, Giger RJ, Ginty DD . Neuropilin is a semaphorin III receptor . Cell . 90 . 4 . 753–62 . August 1997 . 9288754 . 10.1016/S0092-8674(00)80535-8 . 17268123 . free .
• Giger RJ, Urquhart ER, Gillespie SK, Levengood DV, Ginty DD, Kolodkin AL . Neuropilin-2 is a receptor for semaphorin IV: insight into the structural basis of receptor function and specificity . Neuron . 21 . 5 . 1079–92 . November 1998 . 9856463 . 10.1016/S0896-6273(00)80625-X . 18445456 . free .
• Chen H, He Z, Bagri A, Tessier-Lavigne M . Semaphorin-neuropilin interactions underlying sympathetic axon responses to class III semaphorins . Neuron . 21 . 6 . 1283–90 . December 1998 . 9883722 . 10.1016/S0896-6273(00)80648-0 . free .
• Takahashi T, Nakamura F, Jin Z, Kalb RG, Strittmatter SM . Semaphorins A and E act as antagonists of neuropilin-1 and agonists of neuropilin-2 receptors . Nature Neuroscience . 1 . 6 . 487–93 . October 1998 . 10196546 . 10.1038/2203 . 38320889 .
• Rossignol M, Beggs AH, Pierce EA, Klagsbrun M . Human neuropilin-1 and neuropilin-2 map to 10p12 and 2q34, respectively . Genomics . 57 . 3 . 459–60 . May 1999 . 10329017 . 10.1006/geno.1999.5790 .
• Tamagnone L, Artigiani S, Chen H, He Z, Ming GI, Song H, Chedotal A, Winberg ML, Goodman CS, Poo M, Tessier-Lavigne M, Comoglio PM . 6 . Plexins are a large family of receptors for transmembrane, secreted, and GPI-anchored semaphorins in vertebrates . Cell . 99 . 1 . 71–80 . October 1999 . 10520995 . 10.1016/S0092-8674(00)80063-X . 17386412 . free .
• Gluzman-Poltorak Z, Cohen T, Herzog Y, Neufeld G . Neuropilin-2 is a receptor for the vascular endothelial growth factor (VEGF) forms VEGF-145 and VEGF-165 [corrected] . The Journal of Biological Chemistry . 275 . 24 . 18040–5 . June 2000 . 10748121 . 10.1074/jbc.M909259199 . free .
• Handa A, Tokunaga T, Tsuchida T, Lee YH, Kijima H, Yamazaki H, Ueyama Y, Fukuda H, Nakamura M . 6 . Neuropilin-2 expression affects the increased vascularization and is a prognostic factor in osteosarcoma . International Journal of Oncology . 17 . 2 . 291–5 . August 2000 . 10891538 . 10.3892/ijo.17.2.291 .
• Rossignol M, Gagnon ML, Klagsbrun M . Genomic organization of human neuropilin-1 and neuropilin-2 genes: identification and distribution of splice variants and soluble isoforms . Genomics . 70 . 2 . 211–22 . December 2000 . 11112349 . 10.1006/geno.2000.6381 .
• Gluzman-Poltorak Z, Cohen T, Shibuya M, Neufeld G . Vascular endothelial growth factor receptor-1 and neuropilin-2 form complexes . The Journal of Biological Chemistry . 276 . 22 . 18688–94 . June 2001 . 11278319 . 10.1074/jbc.M006909200 . free .
• Cohen T, Gluzman-Poltorak Z, Brodzky A, Meytal V, Sabo E, Misselevich I, Hassoun M, Boss JH, Resnick M, Shneyvas D, Eldar S, Neufeld G . 6 . Neuroendocrine cells along the digestive tract express neuropilin-2 . Biochemical and Biophysical Research Communications . 284 . 2 . 395–403 . June 2001 . 11394892 . 10.1006/bbrc.2001.4958 .
• Herzog Y, Kalcheim C, Kahane N, Reshef R, Neufeld G . Differential expression of neuropilin-1 and neuropilin-2 in arteries and veins . Mechanisms of Development . 109 . 1 . 115–9 . November 2001 . 11677062 . 10.1016/S0925-4773(01)00518-4 . 18341197 .
• Oh H, Takagi H, Otani A, Koyama S, Kemmochi S, Uemura A, Honda Y . Selective induction of neuropilin-1 by vascular endothelial growth factor (VEGF): a mechanism contributing to VEGF-induced angiogenesis . Proceedings of the National Academy of Sciences of the United States of America . 99 . 1 . 383–8 . January 2002 . 11756651 . 117569 . 10.1073/pnas.012074399 . 2002PNAS...99..383O . free .
• Fakhari M, Pullirsch D, Abraham D, Paya K, Hofbauer R, Holzfeind P, Hofmann M, Aharinejad S . 6 . Selective upregulation of vascular endothelial growth factor receptors neuropilin-1 and -2 in human neuroblastoma . Cancer . 94 . 1 . 258–63 . January 2002 . 11815985 . 10.1002/cncr.10177 . 45773136 . free .
• Cohen T, Herzog Y, Brodzky A, Greenson JK, Eldar S, Gluzman-Poltorak Z, Neufeld G, Resnick MB . 6 . Neuropilin-2 is a novel marker expressed in pancreatic islet cells and endocrine pancreatic tumours . The Journal of Pathology . 198 . 1 . 77–82 . September 2002 . 12210066 . 10.1002/path.1179 . 24579823 . free .
• Kawakami T, Tokunaga T, Hatanaka H, Kijima H, Yamazaki H, Abe Y, Osamura Y, Inoue H, Ueyama Y, Nakamura M . 6 . Neuropilin 1 and neuropilin 2 co-expression is significantly correlated with increased vascularity and poor prognosis in nonsmall cell lung carcinoma . Cancer . 95 . 10 . 2196–201 . November 2002 . 12412174 . 10.1002/cncr.10936 . 28744286 .

Notes and References

1. Soker S, Takashima S, Miao HQ, Neufeld G, Klagsbrun M . Neuropilin-1 is expressed by endothelial and tumor cells as an isoform-specific receptor for vascular endothelial growth factor . Cell . 92 . 6 . 735–45 . March 1998 . 9529250 . 10.1016/S0092-8674(00)81402-6 . 547080 . free .
2. Chen H, Chédotal A, He Z, Goodman CS, Tessier-Lavigne M . 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 . Neuron . 19 . 3 . 547–59 . September 1997 . 9331348 . 10.1016/S0896-6273(00)80371-2 . 17985062 . free .
3. Harman. Jennifer L.. Sayers. Jacob. Chapman. Chey. Pellet-Many. Caroline . vanc . 2020-07-21. Emerging Roles for Neuropilin-2 in Cardiovascular Disease . International Journal of Molecular Sciences . 21. 14. 5154. 10.3390/ijms21145154. 32708258. 7404143. free.
4. Kofler N, Simons M . 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 . May 2016 . 26849476 . 4957701 . 10.1097/MOH.0000000000000233 .
5. Peng K, Bai Y, Zhu Q, Hu B, Xu Y . Targeting VEGF-neuropilin interactions: a promising antitumor strategy . Drug Discovery Today . 24 . 2 . 656–664 . February 2019 . 30315890 . 10.1016/j.drudis.2018.10.004 . 52979538 .
6. Kitsukawa T, Shimizu M, Sanbo M, Hirata T, Taniguchi M, Bekku Y, Yagi T, Fujisawa H . Neuropilin-semaphorin III/D-mediated chemorepulsive signals play a crucial role in peripheral nerve projection in mice . Neuron . 19 . 5 . 995–1005 . November 1997 . 9390514 . 10.1016/s0896-6273(00)80392-x . 17769318 . free .
7. Web site: Entrez Gene: NRP2 neuropilin 2.