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Sphingosine 1-Phosphate Signaling via Transporters in Zebrafish and Mice

  • Chapter
Bioactive Lipid Mediators

Abstract

The bioactive lipid mediator sphingosine 1-phosphate (S1P) plays a pivotal role in various cellular functions, such as proliferation, migration, and differentiation. S1P is intracellularly produced by sphingosine kinases and is released from the cells. Subsequently, the secreted S1P associates with S1P receptors (S1PRs) on a target cell surface, causing activation of downstream signaling pathways. The zebrafish (Danio rerio) is widely used as a vertebrate model organism to study the processes of organogenesis and morphogenesis. Spns2 was originally identified as an S1P transporter in zebrafish; Spns2 regulates the migration of cardiac progenitors via the S1PR2 receptor. Murine and human SPNS2 can also transport S1P from the cells. In mice, SPNS2 enables transport of S1P from vascular endothelial cells into the plasma and regulates lymphocyte egress from lymphoid organs. Recent remarkable developments in genome-editing technologies, such as transcription activator-like effector nucleases (TALENs) and the clustered regularly interspaced short palindromic repeats (CRISPR)/CRISPR-associated (Cas)9 system, allow researchers to introduce genomic modifications in various model animals. In this chapter, we review not only the physiological roles of S1P transporters in mammals and zebrafish but also the strategy for generating S1PR-knockout zebrafish using genome-editing technologies.

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References

  1. Wymann MP, Schneiter R (2008) Lipid signalling in disease. Nat Rev Mol Cell Biol 9(2):162–176. doi:10.1038/nrm2335

    Article  CAS  PubMed  Google Scholar 

  2. Brinkmann V (2007) Sphingosine 1-phosphate receptors in health and disease: mechanistic insights from gene deletion studies and reverse pharmacology. Pharmacol Ther 115(1):84–105. doi:10.1016/j.pharmthera.2007.04.006

    Article  CAS  PubMed  Google Scholar 

  3. Hisano Y, Nishi T, Kawahara A (2012) The functional roles of S1P in immunity. J Biochem 152(4):305–311. doi:10.1093/jb/mvs090

    Article  PubMed  Google Scholar 

  4. Strub GM, Maceyka M, Hait NC, Milstien S, Spiegel S (2010) Extracellular and intracellular actions of sphingosine-1-phosphate. Adv Exp Med Biol 688:141–155. doi:10.1007/978-1-4419-6741-1_10

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  5. Olivera A, Spiegel S (1993) Sphingosine-1-phosphate as second messenger in cell proliferation induced by PDGF and FCS mitogens. Nature 365(6446):557–560. doi:10.1038/365557a0

    Article  CAS  PubMed  Google Scholar 

  6. Kihara A, Mitsutake S, Mizutani Y, Igarashi Y (2007) Metabolism and biological functions of two phosphorylated sphingolipids, sphingosine 1-phosphate and ceramide 1-phosphate. Prog Lipid Res 46(2):126–144. doi:10.1016/j.plipres.2007.03.001

    Article  CAS  PubMed  Google Scholar 

  7. Chae SS, Proia RL, Hla T (2004) Constitutive expression of the S1P1 receptor in adult tissues. Prostaglandins Other Lipid Mediat 73(1-2):141–150. doi:10.1016/j.prostaglandins.2004.01.006

    Article  CAS  PubMed  Google Scholar 

  8. Ishii I, Friedman B, Ye X, Kawamura S, McGiffert C, Contos JJ, Kingsbury MA, Zhang G, Brown JH, Chun J (2001) Selective loss of sphingosine 1-phosphate signaling with no obvious phenotypic abnormality in mice lacking its G protein-coupled receptor, LP(B3)/EDG-3. J Biol Chem 276(36):33697–33704. doi:10.1074/jbc.M10441200

    Article  CAS  PubMed  Google Scholar 

  9. Yatomi Y, Ruan F, Hakomori S, Igarashi Y (1995) Sphingosine-1-phosphate: a platelet-activating sphingolipid released from agonist-stimulated human platelets. Blood 86(1):193–202

    CAS  PubMed  Google Scholar 

  10. Herzog BH, Fu J, Wilson SJ, Hess PR, Sen A, McDaniel JM, Pan Y, Sheng M, Yago T, Silasi-Mansat R, McGee S, May F, Nieswandt B, Morris AJ, Lupu F, Coughlin SR, McEver RP, Chen H, Kahn ML, Xia L (2013) Podoplanin maintains high endothelial venule integrity by interacting with platelet CLEC-2. Nature 502(7469):105–109. doi:10.1038/nature12501

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  11. Kobayashi N, Nishi T, Hirata T, Kihara A, Sano T, Igarashi Y, Yamaguchi A (2006) Sphingosine 1-phosphate is released from the cytosol of rat platelets in a carrier-mediated manner. J Lipid Res 47(3):614–621. doi:10.1194/jlr.M500468-JLR200

    Article  CAS  PubMed  Google Scholar 

  12. Hanel P, Andreani P, Graler MH (2007) Erythrocytes store and release sphingosine 1-phosphate in blood. FASEB J 21(4):1202–1209. doi:10.1096/fj.06-7433com

    Article  PubMed  Google Scholar 

  13. Prieschl EE, Csonga R, Novotny V, Kikuchi GE, Baumruker T (1999) The balance between sphingosine and sphingosine-1-phosphate is decisive for mast cell activation after Fc epsilon receptor I triggering. J Exp Med 190(1):1–8. doi:10.1084/jem.190.1.1

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  14. Lee Y-M, Venkataraman K, Hwang S-I, Han DK, Hla T (2007) A novel method to quantify sphingosine 1-phosphate by immobilized metal affinity chromatography (IMAC). Prostaglandins Other Lipid Mediat 84(3-4):154–162. doi:10.1016/j.prostaglandins.2007.08.001

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  15. Bassi R, Anelli V, Giussani P, Tettamanti G, Viani P, Riboni L (2006) Sphingosine-1-phosphate is released by cerebellar astrocytes in response to bFGF and induces astrocyte proliferation through Gi-protein-coupled receptors. Glia 53(6):621–630. doi:10.1002/glia.20324

    Article  PubMed  Google Scholar 

  16. Anelli V, Bassi R, Tettamanti G, Viani P, Riboni L (2005) Extracellular release of newly synthesized sphingosine-1-phosphate by cerebellar granule cells and astrocytes. J Neurochem 92(5):1204–1215. doi:10.1111/j.1471-4159.2004.02955.x

    Article  CAS  PubMed  Google Scholar 

  17. Nieuwenhuis B, Luth A, Chun J, Huwiler A, Pfeilschifter J, Schafer-Korting M, Kleuser B (2009) Involvement of the ABC-transporter ABCC1 and the sphingosine 1-phosphate receptor subtype S1P(3) in the cytoprotection of human fibroblasts by the glucocorticoid dexamethasone. J Mol Med 87(6):645–657. doi:10.1007/s00109-009-0468-x

    Article  CAS  PubMed  Google Scholar 

  18. Tanfin Z, Serrano-Sanchez M, Leiber D (2011) ATP-binding cassette ABCC1 is involved in the release of sphingosine 1-phosphate from rat uterine leiomyoma ELT3 cells and late pregnant rat myometrium. Cell Signal 23(12):1997–2004. doi:10.1016/j.cellsig.2011.07.010

    Article  CAS  PubMed  Google Scholar 

  19. Pappu R, Schwab SR, Cornelissen I, Pereira JP, Regard JB, Xu Y, Camerer E, Zheng Y-W, Huang Y, Cyster JG, Coughlin SR (2007) Promotion of lymphocyte egress into blood and lymph by distinct sources of sphingosine-1-phosphate. Science 316(5822):295–298. doi:10.1126/science.1139221

    Article  CAS  PubMed  Google Scholar 

  20. Hisano Y, Kobayashi N, Yamaguchi A, Nishi T (2012) Mouse SPNS2 functions as a sphingosine-1-phosphate transporter in vascular endothelial cells. PLoS One 7(6), e38941. doi:10.1371/journal.pone.0038941

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  21. Kawahara A, Nishi T, Hisano Y, Fukui H, Yamaguchi A, Mochizuki N (2009) The sphingolipid transporter spns2 functions in migration of zebrafish myocardial precursors. Science 323(5913):524–527. doi:10.1126/science.1167449

    Article  CAS  PubMed  Google Scholar 

  22. Sato K, Malchinkhuu E, Horiuchi Y, Mogi C, Tomura H, Tosaka M, Yoshimoto Y, Kuwabara A, Okajima F (2007) Critical role of ABCA1 transporter in sphingosine 1-phosphate release from astrocytes. J Neurochem 103(6):2610–2619. doi:10.1111/j.1471-4159.2007.04958.x

    CAS  PubMed  Google Scholar 

  23. Honig SM, Fu S, Mao X, Yopp A, Gunn MD, Randolph GJ, Bromberg JS (2003) FTY720 stimulates multidrug transporter- and cysteinyl leukotriene-dependent T cell chemotaxis to lymph nodes. J Clin Invest 111(5):627–637. doi:10.1172/JCI16200

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  24. Mitra P, Oskeritzian CA, Payne SG, Beaven MA, Milstien S, Spiegel S (2006) Role of ABCC1 in export of sphingosine-1-phosphate from mast cells. Proc Natl Acad Sci U S A 103(44):16394–16399. doi:10.1073/pnas.0603734103

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  25. Takabe K, Kim RH, Allegood JC, Mitra P, Ramachandran S, Nagahashi M, Harikumar KB, Hait NC, Milstien S, Spiegel S (2010) Estradiol induces export of sphingosine-1-phosphate from breast cancer cells via ABCC1 and ABCG2. J Biol Chem 285(14):10477–10486. doi:10.1074/jbc.M109.064162

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  26. Kobayashi N, Kobayashi N, Yamaguchi A, Nishi T (2009) Characterization of the ATP-dependent sphingosine 1-phosphate transporter in rat erythrocytes. J Biol Chem 284(32):21192–21200. doi:10.1074/jbc.M109.006163

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  27. Hisano Y, Kobayashi N, Kawahara A, Yamaguchi A, Nishi T (2011) The sphingosine 1-phosphate transporter, SPNS2, functions as a transporter of the phosphorylated form of the immunomodulating agent FTY720. J Biol Chem 286(3):1758–1766. doi:10.1074/jbc.M110.171116

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  28. Fukuhara S, Simmons S, Kawamura S, Inoue A, Orba Y, Tokudome T, Sunden Y, Arai Y, Moriwaki K, Ishida J, Uemura A, Kiyonari H, Abe T, Fukamizu A, Hirashima M, Sawa H, Aoki J, Ishii M, Mochizuki N (2012) The sphingosine-1-phosphate transporter Spns2 expressed on endothelial cells regulates lymphocyte trafficking in mice. J Clin Invest 122(4):1416–1426. doi:10.1172/JCI60746

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  29. Mendoza A, Bréart B, Ramos-Perez WD, Pitt LA, Gobert M, Sunkara M, Lafaille JJ, Morris AJ, Schwab SR (2012) The transporter spns2 is required for secretion of lymph but not plasma sphingosine-1-phosphate. Cell Rep 2(5):1104–1110. doi:10.1016/j.celrep.2012.09.021

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  30. Nagahashi M, Kim EY, Yamada A, Ramachandran S, Allegood JC, Hait NC, Maceyka M, Milstien S, Takabe K, Spiegel S (2013) Spns2, a transporter of phosphorylated sphingoid bases, regulates their blood and lymph levels, and the lymphatic network. FASEB J 27(3):1001–1011. doi:10.1096/fj.12-219618

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  31. Nijnik A, Clare S, Hale C, Chen J, Raisen C, Mottram L, Lucas M, Estabel J, Ryder E, Adissu H, Adams NC, Ramirez-Solis R, White JK, Steel KP, Dougan G, Hancock RE (2012) The role of sphingosine-1-phosphate transporter spns2 in immune system function. J Immunol 189(1):102–111. doi:10.4049/jimmunol.1200282

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  32. Zachariah MA, Cyster JG (2010) Neural crest-derived pericytes promote egress of mature thymocytes at the corticomedullary junction. Science 328(5982):1129–1135. doi:10.1126/science.1188222

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  33. Kupperman E, An S, Osborne N, Waldron S, Stainier DY (2000) A sphingosine-1-phosphate receptor regulates cell migration during vertebrate heart development. Nature 406(6792):192–195. doi:10.1038/35018092

    Article  CAS  PubMed  Google Scholar 

  34. Ye D, Lin F (2013) S1pr2/Galpha13 signaling controls myocardial migration by regulating endoderm convergence. Development 140(4):789–799. doi:10.1242/dev.085340

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  35. Osborne N, Brand-Arzamendi K, Ober EA, Jin S-W, Verkade H, Holtzman NG, Yelon D, Stainier DYR (2008) The spinster homolog, two of hearts, is required for sphingosine 1-phosphate signaling in zebrafish. Curr Biol 18(23):1882–1888. doi:10.1016/j.cub.2008.10.061

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  36. Balczerski B, Matsutani M, Castillo P, Osborne N, Stainier DYR, Crump JG (2012) Analysis of sphingosine-1-phosphate signaling mutants reveals endodermal requirements for the growth but not dorsoventral patterning of jaw skeletal precursors. Dev Biol 362(2):230–241. doi:10.1016/j.ydbio.2011.12.010

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  37. Hisano Y, Ota S, Takada S, Kawahara A (2013) Functional cooperation of spns2 and fibronectin in cardiac and lower jaw development. Biol Open 2(8):789–794. doi:10.1242/bio.20134994

    Article  PubMed Central  PubMed  Google Scholar 

  38. Hisano Y, Ota S, Kawahara A (2014) Genome editing using artificial site-specific nucleases in zebrafish. Dev Growth Differ 56(1):26–33. doi:10.1111/dgd.12094

    Article  CAS  PubMed  Google Scholar 

  39. Gaj T, Gersbach CA, Barbas CF 3rd (2013) ZFN, TALEN, and CRISPR/Cas-based methods for genome engineering. Trends Biotechnol 31(7):397–405. doi:10.1016/j.tibtech.2013.04.004

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  40. Hisano Y, Ota S, Arakawa K, Muraki M, Kono N, Oshita K, Sakuma T, Tomita M, Yamamoto T, Okada Y, Kawahara A (2013) Quantitative assay for TALEN activity at endogenous genomic loci. Biol Open 2(4):363–367. doi:10.1242/bio.20133871

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  41. Ota S, Hisano Y, Muraki M, Hoshijima K, Dahlem TJ, Grunwald DJ, Okada Y, Kawahara A (2013) Efficient identification of TALEN-mediated genome modifications using heteroduplex mobility assays. Genes Cells 18(6):450–458. doi:10.1111/gtc.12050

    Article  CAS  PubMed  Google Scholar 

  42. Robu ME, Larson JD, Nasevicius A, Beiraghi S, Brenner C, Farber SA, Ekker SC (2007) p53 activation by knockdown technologies. PLoS Genet 3(5), e78. doi:10.1371/journal.pgen.0030078

    Article  PubMed Central  PubMed  Google Scholar 

  43. Ben Shoham A, Malkinson G, Krief S, Shwartz Y, Ely Y, Ferrara N, Yaniv K, Zelzer E (2012) S1P1 inhibits sprouting angiogenesis during vascular development. Development. doi:10.1242/dev.078550

    PubMed  Google Scholar 

  44. Gaengel K, Niaudet C, Hagikura K, Lavina B, Muhl L, Hofmann JJ, Ebarasi L, Nystrom S, Rymo S, Chen LL, Pang MF, Jin Y, Raschperger E, Roswall P, Schulte D, Benedito R, Larsson J, Hellstrom M, Fuxe J, Uhlen P, Adams R, Jakobsson L, Majumdar A, Vestweber D, Uv A, Betsholtz C (2012) The sphingosine-1-phosphate receptor S1PR1 restricts sprouting angiogenesis by regulating the interplay between VE-cadherin and VEGFR2. Dev Cell 23(3):587–599. doi:10.1016/j.devcel.2012.08.005

    Article  CAS  PubMed  Google Scholar 

  45. Mendelson K, Zygmunt T, Torres-Vazquez J, Evans T, Hla T (2013) Sphingosine 1-phosphate receptor signaling regulates proper embryonic vascular patterning. J Biol Chem 288(4):2143–2156. doi:10.1074/jbc.M112.427344

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  46. Kobayashi M, Inoue K, Warabi E, Minami T, Kodama T (2005) A simple method of isolating mouse aortic endothelial cells. J Atheroscler Thromb 12(3):138–142. doi:10.5551/jat.12.138

    Article  PubMed  Google Scholar 

  47. Bligh EG, Dyer WJ (1959) A rapid method of total lipid extraction and purification. Can J Physiol Pharmacol 37(8):911–917. doi:10.1139/o59-099

    Article  CAS  Google Scholar 

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Acknowledgements

We thank Drs. S. Ota, N. Kobayashi, and A. Yamaguchi for valuable discussion. This work was supported by the Funding Program for Next Generation World-Leading Researchers (NEXT Program) and by the Japan Society for the Promotion of Science (JSPS).

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Correspondence to Yu Hisano or Atsuo Kawahara .

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Hisano, Y., Nishi, T., Kawahara, A. (2015). Sphingosine 1-Phosphate Signaling via Transporters in Zebrafish and Mice. In: Yokomizo, T., Murakami, M. (eds) Bioactive Lipid Mediators. Springer, Tokyo. https://doi.org/10.1007/978-4-431-55669-5_15

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