R-spondin-1 is a secreted protein that in humans is encoded by the RSPO1 gene, found on chromosome 1.[5] In humans, it interacts with WNT4 in the process of female sex development. Loss of function can cause female to male sex reversal.[6] Furthermore, it promotes canonical WNT/β catenin signaling.[7]
RSPO1 is required for the early development of gonads, regardless of sex. It has been found in mice only eleven days after fertilization.[6] To induce cell proliferation, it acts synergistically with WNT4.[6] They help stabilize β-catenin, which activates downstream targets. If both are deficient in XY mice, there is less expression of SRY and a reduction in the amount of SOX9. Moreover, defects in vascularization are found. These occurrences result in testicular hypoplasia. Male to female sex reversal, however, does not occur because Leydig cells remain normal. They are maintained by steroidogenic cells, now unrepressed.[6]
Ovariesedit
RSPO1 is necessary in female sex development. It augments the WNT/β catenin pathway to oppose male sex development. In critical gonadal stages, between six and nine weeks after fertilization, the ovaries upregulate it while the testes downregulate it.[8]
Oral mucosa has been identified as a target tissue for RSPO1. When administered to normal mice, it causes nuclear translocation of β-catenin to this region.[7] Modulation of the WNT/β catenin pathway occurs through the relief of Dkk1 inhibition. This occurrence results in increased basal cellularity, thickened mucosa, and elevated epithelial cell proliferation in the tongue. RSPO1 can therefore potentially aid in the treatment of mucositis, which is characterized by inflammation of the oral cavity. This unfortunate condition often accompanies chemotherapy and radiation in cancer patients with head and neck tumors.[7] RSPO1 has also been shown to promote gastrointestinal epithelial cell proliferation in mice.[5]
Referencesedit
^ abcGRCh38: Ensembl release 89: ENSG00000169218 - Ensembl, May 2017
^ abcGRCm38: Ensembl release 89: ENSMUSG00000028871 - Ensembl, May 2017
^"Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
^"Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
^ abcdChassot, A. -A.; Bradford, S. T.; Auguste, A.; Gregoire, E. P.; Pailhoux, E.; De Rooij, D. G.; Schedl, A.; Chaboissier, M. -C. (2012). "WNT4 and RSPO1 together are required for cell proliferation in the early mouse gonad". Development. 139 (23): 4461–4472. doi:10.1242/dev.078972. PMID 23095882.
^ abcZhao, J.; Kim, K. -A.; De Vera, J.; Palencia, S.; Wagle, M.; Abo, A. (2009). "R-Spondin1 protects mice from chemotherapy or radiation-induced oral mucositis through the canonical Wnt/ -catenin pathway". Proceedings of the National Academy of Sciences. 106 (7): 2331–2336. doi:10.1073/pnas.0805159106. PMC2650156. PMID 19179402.
^Tomaselli, S.; Megiorni, F.; Lin, L.; Mazzilli, M. C.; Gerrelli, D.; Majore, S.; Grammatico, P.; Achermann, J. C. (2011). Lee, Sean (ed.). "Human RSPO1/R-spondin1 is Expressed during Early Ovary Development and Augments β-Catenin Signaling". PLOS ONE. 6 (1): e16366. Bibcode:2011PLoSO...616366T. doi:10.1371/journal.pone.0016366. PMC3030573. PMID 21297984.
Further readingedit
Strausberg RL, Feingold EA, Grouse LH, et al. (2003). "Generation and initial analysis of more than 15,000 full-length human and mouse cDNA sequences". Proc. Natl. Acad. Sci. U.S.A. 99 (26): 16899–903. Bibcode:2002PNAS...9916899M. doi:10.1073/pnas.242603899. PMC139241. PMID 12477932.
Ota T, Suzuki Y, Nishikawa T, et al. (2004). "Complete sequencing and characterization of 21,243 full-length human cDNAs". Nat. Genet. 36 (1): 40–5. doi:10.1038/ng1285. PMID 14702039.
Kamata T, Katsube K, Michikawa M, et al. (2004). "R-spondin, a novel gene with thrombospondin type 1 domain, was expressed in the dorsal neural tube and affected in Wnts mutants". Biochim. Biophys. Acta. 1676 (1): 51–62. doi:10.1016/j.bbaexp.2003.10.009. PMID 14732490.
Gerhard DS, Wagner L, Feingold EA, et al. (2004). "The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)". Genome Res. 14 (10B): 2121–7. doi:10.1101/gr.2596504. PMC528928. PMID 15489334.
Kim KA, Kakitani M, Zhao J, et al. (2005). "Mitogenic influence of human R-spondin1 on the intestinal epithelium". Science. 309 (5738): 1256–9. Bibcode:2005Sci...309.1256K. doi:10.1126/science.1112521. PMID 16109882. S2CID 45221785.
Abraham C, Cho JH (2005). "Inducing intestinal growth". N. Engl. J. Med. 353 (21): 2297–9. doi:10.1056/NEJMcibr053367. PMID 16306530.
Kimura K, Wakamatsu A, Suzuki Y, et al. (2006). "Diversification of transcriptional modulation: large-scale identification and characterization of putative alternative promoters of human genes". Genome Res. 16 (1): 55–65. doi:10.1101/gr.4039406. PMC1356129. PMID 16344560.
Gregory SG, Barlow KF, McLay KE, et al. (2006). "The DNA sequence and biological annotation of human chromosome 1". Nature. 441 (7091): 315–21. Bibcode:2006Natur.441..315G. doi:10.1038/nature04727. PMID 16710414.
Parma P, Radi O, Vidal V, et al. (2007). "R-spondin1 is essential in sex determination, skin differentiation and malignancy". Nat. Genet. 38 (11): 1304–9. doi:10.1038/ng1907. PMID 17041600. S2CID 9687808.
Binnerts ME, Kim KA, Bright JM, et al. (2007). "R-Spondin1 regulates Wnt signaling by inhibiting internalization of LRP6". Proc. Natl. Acad. Sci. U.S.A. 104 (37): 14700–5. Bibcode:2007PNAS..10414700B. doi:10.1073/pnas.0702305104. PMC1965484. PMID 17804805.
External linksedit
Overview of all the structural information available in the PDB for UniProt: Q2MKA7 (R-spondin-1) at the PDBe-KB.
This article on a gene on human chromosome 1 is a stub. You can help Wikipedia by expanding it.
spondin, spondin, secreted, protein, that, humans, encoded, rspo1, gene, found, chromosome, humans, interacts, with, wnt4, process, female, development, loss, function, cause, female, male, reversal, furthermore, promotes, canonical, catenin, signaling, rspo1a. R spondin 1 is a secreted protein that in humans is encoded by the RSPO1 gene found on chromosome 1 5 In humans it interacts with WNT4 in the process of female sex development Loss of function can cause female to male sex reversal 6 Furthermore it promotes canonical WNT b catenin signaling 7 RSPO1Available structuresPDBOrtholog search PDBe RCSBList of PDB id codes4BSO 4BSP 4BSR 4BSS 4BST 4BSU 4CDK 4KNG 4KT1 4LI2 4QXFIdentifiersAliasesRSPO1 CRISTIN3 RSPO R spondin 1External IDsOMIM 609595 MGI 2183426 HomoloGene 52148 GeneCards RSPO1Gene location Human Chr Chromosome 1 human 1 Band1p34 3Start37 611 350 bp 1 End37 634 892 bp 1 Gene location Mouse Chr Chromosome 4 mouse 2 Band4 4 D2 2Start124 880 223 bp 2 End124 902 892 bp 2 RNA expression patternBgeeHumanMouse ortholog Top expressed incanal of the cervixgerminal epitheliumright uterine tubeleft uterine tubemyometriumsmooth muscle tissuevaginagastric mucosaparietal pleuraperitoneumTop expressed insuperior surface of tonguelensgallbladderpapillary dermisdermal papillavaginasciatic nervefemale urethraejaculatory ductuterusMore reference expression dataBioGPSn aGene ontologyMolecular functionheparin binding signaling receptor binding protein binding G protein coupled receptor binding frizzled bindingCellular componentextracellular region nucleus extracellular spaceBiological processpositive regulation of canonical Wnt signaling pathway positive regulation of Wnt signaling pathway regulation of receptor internalization positive regulation of protein phosphorylation Wnt signaling pathway response to stimulusSources Amigo QuickGOOrthologsSpeciesHumanMouseEntrez284654192199EnsemblENSG00000169218ENSMUSG00000028871UniProtQ2MKA7Q9Z132RefSeq mRNA NM 001038633NM 001242908NM 001242909NM 001242910NM 173640NM 138683RefSeq protein NP 001033722NP 001229837NP 001229838NP 001229839NP 619624Location UCSC Chr 1 37 61 37 63 MbChr 4 124 88 124 9 MbPubMed search 3 4 WikidataView Edit HumanView Edit Mouse Contents 1 Structure 2 Function 2 1 Sex Development 2 1 1 Early Gonads 2 1 2 Ovaries 2 2 Mucositis 3 References 4 Further reading 5 External linksStructure editThe protein has two cysteine rich furin like domains and one thrombospondin type 1 domain 5 Function editSex Development edit Early Gonads edit RSPO1 is required for the early development of gonads regardless of sex It has been found in mice only eleven days after fertilization 6 To induce cell proliferation it acts synergistically with WNT4 6 They help stabilize b catenin which activates downstream targets If both are deficient in XY mice there is less expression of SRY and a reduction in the amount of SOX9 Moreover defects in vascularization are found These occurrences result in testicular hypoplasia Male to female sex reversal however does not occur because Leydig cells remain normal They are maintained by steroidogenic cells now unrepressed 6 Ovaries edit RSPO1 is necessary in female sex development It augments the WNT b catenin pathway to oppose male sex development In critical gonadal stages between six and nine weeks after fertilization the ovaries upregulate it while the testes downregulate it 8 Mucositis edit Oral mucosa has been identified as a target tissue for RSPO1 When administered to normal mice it causes nuclear translocation of b catenin to this region 7 Modulation of the WNT b catenin pathway occurs through the relief of Dkk1 inhibition This occurrence results in increased basal cellularity thickened mucosa and elevated epithelial cell proliferation in the tongue RSPO1 can therefore potentially aid in the treatment of mucositis which is characterized by inflammation of the oral cavity This unfortunate condition often accompanies chemotherapy and radiation in cancer patients with head and neck tumors 7 RSPO1 has also been shown to promote gastrointestinal epithelial cell proliferation in mice 5 References edit a b c GRCh38 Ensembl release 89 ENSG00000169218 Ensembl May 2017 a b c GRCm38 Ensembl release 89 ENSMUSG00000028871 Ensembl May 2017 Human PubMed Reference National Center for Biotechnology Information U S National Library of Medicine Mouse PubMed Reference National Center for Biotechnology Information U S National Library of Medicine a b c Entrez Gene RSPO1 R spondin homolog Xenopus laevis a b c d Chassot A A Bradford S T Auguste A Gregoire E P Pailhoux E De Rooij D G Schedl A Chaboissier M C 2012 WNT4 and RSPO1 together are required for cell proliferation in the early mouse gonad Development 139 23 4461 4472 doi 10 1242 dev 078972 PMID 23095882 a b c Zhao J Kim K A De Vera J Palencia S Wagle M Abo A 2009 R Spondin1 protects mice from chemotherapy or radiation induced oral mucositis through the canonical Wnt catenin pathway Proceedings of the National Academy of Sciences 106 7 2331 2336 doi 10 1073 pnas 0805159106 PMC 2650156 PMID 19179402 Tomaselli S Megiorni F Lin L Mazzilli M C Gerrelli D Majore S Grammatico P Achermann J C 2011 Lee Sean ed Human RSPO1 R spondin1 is Expressed during Early Ovary Development and Augments b Catenin Signaling PLOS ONE 6 1 e16366 Bibcode 2011PLoSO 616366T doi 10 1371 journal pone 0016366 PMC 3030573 PMID 21297984 Further reading editStrausberg RL Feingold EA Grouse LH et al 2003 Generation and initial analysis of more than 15 000 full length human and mouse cDNA sequences Proc Natl Acad Sci U S A 99 26 16899 903 Bibcode 2002PNAS 9916899M doi 10 1073 pnas 242603899 PMC 139241 PMID 12477932 Ota T Suzuki Y Nishikawa T et al 2004 Complete sequencing and characterization of 21 243 full length human cDNAs Nat Genet 36 1 40 5 doi 10 1038 ng1285 PMID 14702039 Kamata T Katsube K Michikawa M et al 2004 R spondin a novel gene with thrombospondin type 1 domain was expressed in the dorsal neural tube and affected in Wnts mutants Biochim Biophys Acta 1676 1 51 62 doi 10 1016 j bbaexp 2003 10 009 PMID 14732490 Gerhard DS Wagner L Feingold EA et al 2004 The status quality and expansion of the NIH full length cDNA project the Mammalian Gene Collection MGC Genome Res 14 10B 2121 7 doi 10 1101 gr 2596504 PMC 528928 PMID 15489334 Kim KA Kakitani M Zhao J et al 2005 Mitogenic influence of human R spondin1 on the intestinal epithelium Science 309 5738 1256 9 Bibcode 2005Sci 309 1256K doi 10 1126 science 1112521 PMID 16109882 S2CID 45221785 Abraham C Cho JH 2005 Inducing intestinal growth N Engl J Med 353 21 2297 9 doi 10 1056 NEJMcibr053367 PMID 16306530 Kimura K Wakamatsu A Suzuki Y et al 2006 Diversification of transcriptional modulation large scale identification and characterization of putative alternative promoters of human genes Genome Res 16 1 55 65 doi 10 1101 gr 4039406 PMC 1356129 PMID 16344560 Gregory SG Barlow KF McLay KE et al 2006 The DNA sequence and biological annotation of human chromosome 1 Nature 441 7091 315 21 Bibcode 2006Natur 441 315G doi 10 1038 nature04727 PMID 16710414 Parma P Radi O Vidal V et al 2007 R spondin1 is essential in sex determination skin differentiation and malignancy Nat Genet 38 11 1304 9 doi 10 1038 ng1907 PMID 17041600 S2CID 9687808 Binnerts ME Kim KA Bright JM et al 2007 R Spondin1 regulates Wnt signaling by inhibiting internalization of LRP6 Proc Natl Acad Sci U S A 104 37 14700 5 Bibcode 2007PNAS 10414700B doi 10 1073 pnas 0702305104 PMC 1965484 PMID 17804805 External links editOverview of all the structural information available in the PDB for UniProt Q2MKA7 R spondin 1 at the PDBe KB nbsp This article on a gene on human chromosome 1 is a stub You can help Wikipedia by expanding it vte Retrieved from https en wikipedia org w index php title R spondin 1 amp oldid 1180277649, wikipedia, wiki, book, books, library,
