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. 1996 May 15;15(10):2388–2392.

Sphingosine-1-phosphate rapidly induces Rho-dependent neurite retraction: action through a specific cell surface receptor.

F R Postma 1, K Jalink 1, T Hengeveld 1, W H Moolenaar 1
PMCID: PMC450169  PMID: 8665846

Abstract

Sphingosine-1-phosphate (S1P) is a bioactive lysosphingolipid implicated in mitogenesis and cytoskeletal remodelling, but its mechanism of action is poorly understood. We report here that in N1E-115 neuronal cells, S1P mimics the G protein-coupled receptor agonist lysophosphatidic acid (LPA) in rapidly inducing neurite retraction and soma rounding, a process driven by Rho-dependent contraction of the actin cytoskeleton. S1P is approximately 100-fold more potent than LPA in evoking these shape changes, with an EC50 as low as 1.5 nM. Microinjection of S1P has no effect, neither has addition of sphingosine or ceramide. As with LPA, S1P action is inhibited by suramin and subject to homologous desensitization; however, the responses to S1P and LPA do not show cross-desensitization. We conclude that S1P activates its own high affinity receptor to trigger Rho-regutated cytoskeletal events. Thus, S1P and LPA may belong to an emerging family of bioactive lysophospholipids that act through distinct G protein-coupled receptors to mediate similar actions.

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Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Bornfeldt K. E., Graves L. M., Raines E. W., Igarashi Y., Wayman G., Yamamura S., Yatomi Y., Sidhu J. S., Krebs E. G., Hakomori S. Sphingosine-1-phosphate inhibits PDGF-induced chemotaxis of human arterial smooth muscle cells: spatial and temporal modulation of PDGF chemotactic signal transduction. J Cell Biol. 1995 Jul;130(1):193–206. doi: 10.1083/jcb.130.1.193. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Buhl A. M., Johnson N. L., Dhanasekaran N., Johnson G. L. G alpha 12 and G alpha 13 stimulate Rho-dependent stress fiber formation and focal adhesion assembly. J Biol Chem. 1995 Oct 20;270(42):24631–24634. doi: 10.1074/jbc.270.42.24631. [DOI] [PubMed] [Google Scholar]
  3. Durieux M. E., Carlisle S. J., Salafranca M. N., Lynch K. R. Responses to sphingosine-1-phosphate in X. laevis oocytes: similarities with lysophosphatidic acid signaling. Am J Physiol. 1993 May;264(5 Pt 1):C1360–C1364. doi: 10.1152/ajpcell.1993.264.5.C1360. [DOI] [PubMed] [Google Scholar]
  4. Durieux M. E., Lynch K. R. Signalling properties of lysophosphatidic acid. Trends Pharmacol Sci. 1993 Jun;14(6):249–254. doi: 10.1016/0165-6147(93)90021-b. [DOI] [PubMed] [Google Scholar]
  5. Eichholtz T., Jalink K., Fahrenfort I., Moolenaar W. H. The bioactive phospholipid lysophosphatidic acid is released from activated platelets. Biochem J. 1993 May 1;291(Pt 3):677–680. doi: 10.1042/bj2910677. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Ghosh T. K., Bian J., Gill D. L. Intracellular calcium release mediated by sphingosine derivatives generated in cells. Science. 1990 Jun 29;248(4963):1653–1656. doi: 10.1126/science.2163543. [DOI] [PubMed] [Google Scholar]
  7. Hannun Y. A., Bell R. M. Functions of sphingolipids and sphingolipid breakdown products in cellular regulation. Science. 1989 Jan 27;243(4890):500–507. doi: 10.1126/science.2643164. [DOI] [PubMed] [Google Scholar]
  8. Hannun Y. A. The sphingomyelin cycle and the second messenger function of ceramide. J Biol Chem. 1994 Feb 4;269(5):3125–3128. [PubMed] [Google Scholar]
  9. Jalink K., Eichholtz T., Postma F. R., van Corven E. J., Moolenaar W. H. Lysophosphatidic acid induces neuronal shape changes via a novel, receptor-mediated signaling pathway: similarity to thrombin action. Cell Growth Differ. 1993 Apr;4(4):247–255. [PubMed] [Google Scholar]
  10. Jalink K., Hengeveld T., Mulder S., Postma F. R., Simon M. F., Chap H., van der Marel G. A., van Boom J. H., van Blitterswijk W. J., Moolenaar W. H. Lysophosphatidic acid-induced Ca2+ mobilization in human A431 cells: structure-activity analysis. Biochem J. 1995 Apr 15;307(Pt 2):609–616. doi: 10.1042/bj3070609. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Jalink K., Hordijk P. L., Moolenaar W. H. Growth factor-like effects of lysophosphatidic acid, a novel lipid mediator. Biochim Biophys Acta. 1994 Dec 30;1198(2-3):185–196. doi: 10.1016/0304-419x(94)90013-2. [DOI] [PubMed] [Google Scholar]
  12. Jalink K., Moolenaar W. H. Thrombin receptor activation causes rapid neural cell rounding and neurite retraction independent of classic second messengers. J Cell Biol. 1992 Jul;118(2):411–419. doi: 10.1083/jcb.118.2.411. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. Jalink K., van Corven E. J., Hengeveld T., Morii N., Narumiya S., Moolenaar W. H. Inhibition of lysophosphatidate- and thrombin-induced neurite retraction and neuronal cell rounding by ADP ribosylation of the small GTP-binding protein Rho. J Cell Biol. 1994 Aug;126(3):801–810. doi: 10.1083/jcb.126.3.801. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. Jalink K., van Corven E. J., Moolenaar W. H. Lysophosphatidic acid, but not phosphatidic acid, is a potent Ca2(+)-mobilizing stimulus for fibroblasts. Evidence for an extracellular site of action. J Biol Chem. 1990 Jul 25;265(21):12232–12239. [PubMed] [Google Scholar]
  15. Kolesnick R. Ceramide: a novel second messenger. Trends Cell Biol. 1992 Aug;2(8):232–236. doi: 10.1016/0962-8924(92)90310-j. [DOI] [PubMed] [Google Scholar]
  16. Mattie M., Brooker G., Spiegel S. Sphingosine-1-phosphate, a putative second messenger, mobilizes calcium from internal stores via an inositol trisphosphate-independent pathway. J Biol Chem. 1994 Feb 4;269(5):3181–3188. [PubMed] [Google Scholar]
  17. Michell R. H., Wakelam M. J. Second messengers. Sphingolipid signalling. Curr Biol. 1994 Apr 1;4(4):370–373. doi: 10.1016/s0960-9822(00)00083-x. [DOI] [PubMed] [Google Scholar]
  18. Moolenaar W. H. LPA: a novel lipid mediator with diverse biological actions. Trends Cell Biol. 1994 Jun;4(6):213–219. doi: 10.1016/0962-8924(94)90144-9. [DOI] [PubMed] [Google Scholar]
  19. Moolenaar W. H. Lysophosphatidic acid, a multifunctional phospholipid messenger. J Biol Chem. 1995 Jun 2;270(22):12949–12952. doi: 10.1074/jbc.270.22.12949. [DOI] [PubMed] [Google Scholar]
  20. Olivera A., Spiegel S. Sphingosine-1-phosphate as second messenger in cell proliferation induced by PDGF and FCS mitogens. Nature. 1993 Oct 7;365(6446):557–560. doi: 10.1038/365557a0. [DOI] [PubMed] [Google Scholar]
  21. Ridley A. J., Hall A. Signal transduction pathways regulating Rho-mediated stress fibre formation: requirement for a tyrosine kinase. EMBO J. 1994 Jun 1;13(11):2600–2610. doi: 10.1002/j.1460-2075.1994.tb06550.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  22. Ridley A. J., Hall A. The small GTP-binding protein rho regulates the assembly of focal adhesions and actin stress fibers in response to growth factors. Cell. 1992 Aug 7;70(3):389–399. doi: 10.1016/0092-8674(92)90163-7. [DOI] [PubMed] [Google Scholar]
  23. Sadahira Y., Ruan F., Hakomori S., Igarashi Y. Sphingosine 1-phosphate, a specific endogenous signaling molecule controlling cell motility and tumor cell invasiveness. Proc Natl Acad Sci U S A. 1992 Oct 15;89(20):9686–9690. doi: 10.1073/pnas.89.20.9686. [DOI] [PMC free article] [PubMed] [Google Scholar]
  24. Spiegel S., Milstien S. Sphingolipid metabolites: members of a new class of lipid second messengers. J Membr Biol. 1995 Aug;146(3):225–237. doi: 10.1007/BF00233943. [DOI] [PubMed] [Google Scholar]
  25. Tigyi G., Miledi R. Lysophosphatidates bound to serum albumin activate membrane currents in Xenopus oocytes and neurite retraction in PC12 pheochromocytoma cells. J Biol Chem. 1992 Oct 25;267(30):21360–21367. [PubMed] [Google Scholar]
  26. Wu J., Spiegel S., Sturgill T. W. Sphingosine 1-phosphate rapidly activates the mitogen-activated protein kinase pathway by a G protein-dependent mechanism. J Biol Chem. 1995 May 12;270(19):11484–11488. doi: 10.1074/jbc.270.19.11484. [DOI] [PubMed] [Google Scholar]
  27. Yatomi Y., Ruan F., Hakomori S., Igarashi Y. Sphingosine-1-phosphate: a platelet-activating sphingolipid released from agonist-stimulated human platelets. Blood. 1995 Jul 1;86(1):193–202. [PubMed] [Google Scholar]
  28. Zhang H., Desai N. N., Olivera A., Seki T., Brooker G., Spiegel S. Sphingosine-1-phosphate, a novel lipid, involved in cellular proliferation. J Cell Biol. 1991 Jul;114(1):155–167. doi: 10.1083/jcb.114.1.155. [DOI] [PMC free article] [PubMed] [Google Scholar]
  29. van Corven E. J., van Rijswijk A., Jalink K., van der Bend R. L., van Blitterswijk W. J., Moolenaar W. H. Mitogenic action of lysophosphatidic acid and phosphatidic acid on fibroblasts. Dependence on acyl-chain length and inhibition by suramin. Biochem J. 1992 Jan 1;281(Pt 1):163–169. doi: 10.1042/bj2810163. [DOI] [PMC free article] [PubMed] [Google Scholar]
  30. van der Bend R. L., Brunner J., Jalink K., van Corven E. J., Moolenaar W. H., van Blitterswijk W. J. Identification of a putative membrane receptor for the bioactive phospholipid, lysophosphatidic acid. EMBO J. 1992 Jul;11(7):2495–2501. doi: 10.1002/j.1460-2075.1992.tb05314.x. [DOI] [PMC free article] [PubMed] [Google Scholar]

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