PT - JOURNAL ARTICLE AU - C. Jaillard AU - S. Harrison AU - B. Stankoff AU - M. S. Aigrot AU - A. R. Calver AU - G. Duddy AU - F. S. Walsh AU - M. N. Pangalos AU - N. Arimura AU - K. Kaibuchi AU - B. Zalc AU - C. Lubetzki TI - Edg8/S1P5: An Oligodendroglial Receptor with Dual Function on Process Retraction and Cell Survival AID - 10.1523/JNEUROSCI.4645-04.2005 DP - 2005 Feb 09 TA - The Journal of Neuroscience PG - 1459--1469 VI - 25 IP - 6 4099 - http://www.jneurosci.org/content/25/6/1459.short 4100 - http://www.jneurosci.org/content/25/6/1459.full SO - J. Neurosci.2005 Feb 09; 25 AB - Endothelial differentiation gene (Edg) proteins are G-protein-coupled receptors activated by lysophospholipid mediators: sphingosine-1-phosphate (S1P) or lysophosphatidic acid. We show that in the CNS, expression of Edg8/S1P5, a high-affinity S1P receptor, is restricted to oligodendrocytes and expressed throughout development from the immature stages to the mature myelin-forming cell. S1P activation of Edg8/S1P5 on O4-positive pre-oligodendrocytes induced process retraction via a Rho kinase/collapsin response-mediated protein signaling pathway, whereas no retraction was elicited by S1P on these cells derived from Edg8/S1P5-deficient mice. Edg8/S1P5-mediated process retraction was restricted to immature cells and was no longer observed at later developmental stages. In contrast, S1P activation promoted the survival of mature oligodendrocytes but not of pre-oligodendrocytes. The S1P-induced survival of mature oligodendrocytes was mediated through a pertussis toxin-sensitive, Akt-dependent pathway. Our data demonstrate that Edg8/S1P5 activation on oligodendroglial cells modulates two distinct functional pathways mediating either process retraction or cell survival and that these effects depend on the developmental stage of the cell.