Neuropilina 1
| NRP1 | |||
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| Estruturas dispoñibles | |||
| PDB | Buscar ortólogos: PDBe, RCSB | ||
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| Nomenclatura | Outros nomes
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| Símbolos | NRP1 (HGNC: 8004) NRP1, BDCA4, CD304, NP1, NRP, VEGF165R, Neuropilina 1 | ||
| Identificadores externos | |||
| Locus | Cr. 10 p11.22 | ||
| Padrón de expresión de ARNm | |||
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| Ensembl |
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| RefSeq (ARNm) |
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| RefSeq (proteína) NCBI |
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A neuroplinia 1 ou neuropilina-1 é unha proteína que nos humanos está codificada no xene NRP1 do cromosoma 10.[1][2][3] Nos humanos o xene da neuroplilina 1 está situado no locus 10p11.22. Esta é unha das neuropilinas humanas, xa que existe tamén a neuropilina 2.
Función
[editar | editar a fonte]A NRP1 é un correceptor que está unido á membrana e a un receptor tirosina quinase, que se une tanto ao factor de crecemento endotelial vascular (VEGF; MIM 192240) coma a membros da familia da semaforina (ver SEMA3A; MIM 603961). A NRP1 desempeña funcións versátiles na anxioxénese, guía dos axóns no seu crecemento, supervivencia, migración e invasión celular.[3]
Interaccións
[editar | editar a fonte]A neuropilina 1 interacciona co VEGF-A.[1][4]
Papel na COVID-19
[editar | editar a fonte]A neuropilina 1 facilita a entrada do virus SARS-CoV-2, axenta causante da COVID-19, nas células, o que a fai unha posible diana para futuros fármacos antivirais.[5][6]
Implicación no cancro
[editar | editar a fonte]A neuropilina 1 foi implicada na vascularización e progresión de cancros. A expresión da NRP1 é elevada en mostras de diversos tumores humanos, como cánceres os de cerebro, próstata, mama, colon e pulmón e os niveis de NRP1 están positivamente correlacionados coa metástase.[7][8][9][10][11][12]
No cancro de próstata o xene NRP1 demostrou ser un xene suprimido por andróxenos, regulado á alza durante a resposta adaptativa de tumores de próstata a terapias que actúan sobre os andróxenos e un biomarcador para o prognóstico da metástase e o cancro de próstata mortal.[7] Estudos feitos en ratos in vitro e in vivo mostraron que a NRP1 unida á membrana é proanxioxénica e que promove a vascularización de tumores de próstata.[13]
A expresión elevada de NRP1 está tamén correlacionada coa invasividade de cancro de células pulmonares non pequenas tanto in vitro coma in vivo.[12]
Diana para terapias contra o cancro
[editar | editar a fonte]Como correceptor para o VEGF a NRP1 é unha diana potencial para as terapias anticancerosas. Un péptido sintético, EG3287, xerado en 2005 bloquea a actividade da NRP1.[14] O EG3287 induce a apoptose en células tumorais con elevada expresión de NRP1.[14] Aprobouse unha patente para o EG3287 en 2003.[15] En 2015 non había ensaios clínicos en marcha ou rematados para o EG3287 como terapia para o cancro humano.
A NRP1 soluble ten o efecto oposto á NRP1 unida á membrana e ten actividade anti-VEGF. Os estudos en ratos in vivo indicaron que as inxeccións de sNRP-1 (neuropilina 1 soluble) inhiben a progresión da leucemia mieloide aguda en ratos.[16]
Notas
[editar | editar a fonte]- ↑ 1,0 1,1 Soker S, Takashima S, Miao HQ, Neufeld G, Klagsbrun M (marzo de 1998). "Neuropilin-1 is expressed by endothelial and tumor cells as an isoform-specific receptor for vascular endothelial growth factor". Cell 92 (6): 735–45. PMID 9529250. doi:10.1016/S0092-8674(00)81402-6.
- ↑ Chen H, Chédotal A, He Z, Goodman CS, Tessier-Lavigne M (setembro de 1997). "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. PMID 9331348. doi:10.1016/S0896-6273(00)80371-2.
- ↑ 3,0 3,1 "Entrez Gene: NRP1 neuropilin 1".
- ↑ Mamluk R, Gechtman Z, Kutcher ME, Gasiunas N, Gallagher J, Klagsbrun M (xullo de 2002). "Neuropilin-1 binds vascular endothelial growth factor 165, placenta growth factor-2, and heparin via its b1b2 domain". The Journal of Biological Chemistry 277 (27): 24818–25. PMID 11986311. doi:10.1074/jbc.M200730200.
- ↑ Cantuti-Castelvetri, Ludovico; Ojha, Ravi; Pedro, Liliana D.; Djannatian, Minou; Franz, Jonas; Kuivanen, Suvi; Meer, Franziska van der; Kallio, Katri; Kaya, Tuğberk; Anastasina, Maria; Smura, Teemu; Levanov, Lev; Szirovicza, Leonora; Tobi, Allan; Kallio-Kokko, Hannimari; Österlund, Pamela; Joensuu, Merja; Meunier, Frédéric A.; Butcher, Sarah J.; Winkler, Martin Sebastian; Mollenhauer, Brit; Helenius, Ari; Gokce, Ozgun; Teesalu, Tambet; Hepojoki, Jussi; Vapalahti, Olli; Stadelmann, Christine; Balistreri, Giuseppe; Simons, Mikael (13 novembro de 2020). "Neuropilin-1 facilitates SARS-CoV-2 cell entry and infectivity". Science 370 (6518): 856–860. PMC 7857391. PMID 33082293. doi:10.1126/science.abd2985.
- ↑ "Neuropilin-1 drives SARS-CoV-2 infectivity, finds breakthrough study". MedicalXpress.
- ↑ 7,0 7,1 Tse BW, Volpert M, Ratther E, Stylianou N, Nouri M, McGowan K, Lehman ML, McPherson SJ, Roshan-Moniri M, Butler MS, Caradec J, Gregory-Evans CY, McGovern J, Das R, Takhar M, Erho N, Alshalafa M, Davicioni E, Schaeffer EM, Jenkins RB, Ross AE, Karnes RJ, Den RB, Fazli L, Gregory PA, Gleave ME, Williams ED, Rennie PS, Buttyan R, Gunter JH, Selth LA, Russell PJ, Nelson CC, Hollier BG (xaneiro de 2017). "Neuropilin-1 is upregulated in the adaptive response of prostate tumors to androgen-targeted therapies and is prognostic of metastatic progression and patient mortality". Oncogene 36 (24): 3417–3427. PMC 5485179. PMID 28092670. doi:10.1038/onc.2016.482.
- ↑ Fakhari M, Pullirsch D, Abraham D, Paya K, Hofbauer R, Holzfeind P, Hofmann M, Aharinejad S (xaneiro de 2002). "Selective upregulation of vascular endothelial growth factor receptors neuropilin-1 and -2 in human neuroblastoma". Cancer 94 (1): 258–63. PMID 11815985. doi:10.1002/cncr.10177.
- ↑ Latil A, Bièche I, Pesche S, Valéri A, Fournier G, Cussenot O, Lidereau R (marzo de 2000). "VEGF overexpression in clinically localized prostate tumors and neuropilin-1 overexpression in metastatic forms". International Journal of Cancer 89 (2): 167–71. PMID 10754495. doi:10.1002/(SICI)1097-0215(20000320)89:2<167::AID-IJC11>3.0.CO;2-9.
- ↑ Bachelder RE, Crago A, Chung J, Wendt MA, Shaw LM, Robinson G, Mercurio AM (agosto de 2001). "Vascular endothelial growth factor is an autocrine survival factor for neuropilin-expressing breast carcinoma cells". Cancer Research 61 (15): 5736–40. PMID 11479209.
- ↑ Parikh AA, Fan F, Liu WB, Ahmad SA, Stoeltzing O, Reinmuth N, Bielenberg D, Bucana CD, Klagsbrun M, Ellis LM (xuño de 2004). "Neuropilin-1 in human colon cancer: expression, regulation, and role in induction of angiogenesis". The American Journal of Pathology 164 (6): 2139–51. PMC 1615754. PMID 15161648. doi:10.1016/s0002-9440(10)63772-8.
- ↑ 12,0 12,1 Hong TM, Chen YL, Wu YY, Yuan A, Chao YC, Chung YC, Wu MH, Yang SC, Pan SH, Shih JY, Chan WK, Yang PC (agosto de 2007). "Targeting neuropilin 1 as an antitumor strategy in lung cancer". Clinical Cancer Research 13 (16): 4759–68. PMID 17699853. doi:10.1158/1078-0432.CCR-07-0001.
- ↑ Miao HQ, Lee P, Lin H, Soker S, Klagsbrun M (decembro de 2000). "Neuropilin-1 expression by tumor cells promotes tumor angiogenesis and progression". FASEB Journal 14 (15): 2532–9. PMID 11099472. doi:10.1096/fj.00-0250com.
- ↑ 14,0 14,1 Barr MP, Byrne AM, Duffy AM, Condron CM, Devocelle M, Harriott P, Bouchier-Hayes DJ, Harmey JH (xaneiro de 2005). "A peptide corresponding to the neuropilin-1-binding site on VEGF(165) induces apoptosis of neuropilin-1-expressing breast tumour cells". British Journal of Cancer 92 (2): 328–33. PMC 2361857. PMID 15655556. doi:10.1038/sj.bjc.6602308.
- ↑ "Vegf peptides and their use (WO 2003082918 A1)" (patente). 9 de outubro de 2003.
- ↑ Gagnon ML, Bielenberg DR, Gechtman Z, Miao HQ, Takashima S, Soker S, Klagsbrun M (marzo de 2000). "Identification of a natural soluble neuropilin-1 that binds vascular endothelial growth factor: In vivo expression and antitumor activity". Proceedings of the National Academy of Sciences of the United States of America 97 (6): 2573–8. Bibcode:2000PNAS...97.2573G. PMC 15970. PMID 10688880. doi:10.1073/pnas.040337597.
Véxase tamén
[editar | editar a fonte]Bibliografía
[editar | editar a fonte]- Zachary I, Gliki G (febreiro de 2001). "Signaling transduction mechanisms mediating biological actions of the vascular endothelial growth factor family". Cardiovascular Research 49 (3): 568–81. PMID 11166270. doi:10.1016/S0008-6363(00)00268-6.
- He Z, Tessier-Lavigne M (agosto de 1997). "Neuropilin is a receptor for the axonal chemorepellent Semaphorin III". Cell 90 (4): 739–51. PMID 9288753. doi:10.1016/S0092-8674(00)80534-6.
- Giger RJ, Urquhart ER, Gillespie SK, Levengood DV, Ginty DD, Kolodkin AL (novembro de 1998). "Neuropilin-2 is a receptor for semaphorin IV: insight into the structural basis of receptor function and specificity". Neuron 21 (5): 1079–92. PMID 9856463. doi:10.1016/S0896-6273(00)80625-X.
- Chen H, He Z, Bagri A, Tessier-Lavigne M (decembro de 1998). "Semaphorin-neuropilin interactions underlying sympathetic axon responses to class III semaphorins". Neuron 21 (6): 1283–90. PMID 9883722. doi:10.1016/S0896-6273(00)80648-0.
- Takahashi T, Nakamura F, Jin Z, Kalb RG, Strittmatter SM (outubro de 1998). "Semaphorins A and E act as antagonists of neuropilin-1 and agonists of neuropilin-2 receptors". Nature Neuroscience 1 (6): 487–93. PMID 10196546. doi:10.1038/2203.
- Rossignol M, Beggs AH, Pierce EA, Klagsbrun M (maio de 1999). "Human neuropilin-1 and neuropilin-2 map to 10p12 and 2q34, respectively". Genomics 57 (3): 459–60. PMID 10329017. doi:10.1006/geno.1999.5790.
- Makinen T, Olofsson B, Karpanen T, Hellman U, Soker S, Klagsbrun M, Eriksson U, Alitalo K (xullo de 1999). "Differential binding of vascular endothelial growth factor B splice and proteolytic isoforms to neuropilin-1". The Journal of Biological Chemistry 274 (30): 21217–22. PMID 10409677. doi:10.1074/jbc.274.30.21217.
- Cai H, Reed RR (agosto de 1999). "Cloning and characterization of neuropilin-1-interacting protein: a PSD-95/Dlg/ZO-1 domain-containing protein that interacts with the cytoplasmic domain of neuropilin-1". The Journal of Neuroscience 19 (15): 6519–27. PMC 6782790. PMID 10414980. doi:10.1523/JNEUROSCI.19-15-06519.1999.
- Takahashi T, Fournier A, Nakamura F, Wang LH, Murakami Y, Kalb RG, Fujisawa H, Strittmatter SM (outubro de 1999). "Plexin-neuropilin-1 complexes form functional semaphorin-3A receptors". Cell 99 (1): 59–69. PMID 10520994. doi:10.1016/S0092-8674(00)80062-8.
- 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 (outubro de 1999). "Plexins are a large family of receptors for transmembrane, secreted, and GPI-anchored semaphorins in vertebrates". Cell 99 (1): 71–80. PMID 10520995. doi:10.1016/S0092-8674(00)80063-X.
- Gagnon ML, Bielenberg DR, Gechtman Z, Miao HQ, Takashima S, Soker S, Klagsbrun M (marzo de 2000). "Identification of a natural soluble neuropilin-1 that binds vascular endothelial growth factor: In vivo expression and antitumor activity". Proceedings of the National Academy of Sciences of the United States of America 97 (6): 2573–8. Bibcode:2000PNAS...97.2573G. PMC 15970. PMID 10688880. doi:10.1073/pnas.040337597.
- Gluzman-Poltorak Z, Cohen T, Herzog Y, Neufeld G (xuño de 2000). "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. PMID 10748121. doi:10.1074/jbc.M909259199.
- Fuh G, Garcia KC, de Vos AM (setembro de 2000). "The interaction of neuropilin-1 with vascular endothelial growth factor and its receptor flt-1". The Journal of Biological Chemistry 275 (35): 26690–5. PMID 10842181. doi:10.1074/jbc.M003955200.
- Rossignol M, Gagnon ML, Klagsbrun M (decembro de 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. PMID 11112349. doi:10.1006/geno.2000.6381.
- Simpson JC, Wellenreuther R, Poustka A, Pepperkok R, Wiemann S (setembro de 2000). "Systematic subcellular localization of novel proteins identified by large-scale cDNA sequencing". EMBO Reports 1 (3): 287–92. PMC 1083732. PMID 11256614. doi:10.1093/embo-reports/kvd058.
- Whitaker GB, Limberg BJ, Rosenbaum JS (xullo de 2001). "Vascular endothelial growth factor receptor-2 and neuropilin-1 form a receptor complex that is responsible for the differential signaling potency of VEGF(165) and VEGF(121)". The Journal of Biological Chemistry 276 (27): 25520–31. PMID 11333271. doi:10.1074/jbc.M102315200.
- Walter JW, North PE, Waner M, Mizeracki A, Blei F, Walker JW, Reinisch JF, Marchuk DA (marzo de 2002). "Somatic mutation of vascular endothelial growth factor receptors in juvenile hemangioma". Genes, Chromosomes & Cancer 33 (3): 295–303. PMID 11807987. doi:10.1002/gcc.10028.
