Edg8/S1P5: An Oligodendroglial Receptor with Dual Function on Process Retraction and Cell Survival

• Published in: The Journal of neuroscience Vol. 25; no. 6; pp. 1459 - 1469
• Main Authors: Jaillard, C, Harrison, S, Stankoff, B, Aigrot, M. S, Calver, A. R, Duddy, G, Walsh, F. S, Pangalos, M. N, Arimura, N, Kaibuchi, K, Zalc, B, Lubetzki, C
• Format: Journal Article
• Language: English
• Published: United States Soc Neuroscience 09-02-2005; Society for Neuroscience
• Subjects: Amino Acid Sequence; Animals; Ankyrins - analysis; Brain - cytology; Brain - growth & development; Brain Chemistry; Cell Differentiation; Cell Lineage; Cell Shape - drug effects; Cell Surface Extensions - drug effects; Cell Surface Extensions - physiology; Cell Survival - drug effects; Cells, Cultured - drug effects; Cells, Cultured - metabolism; Cells, Cultured - ultrastructure; Cellular/Molecular; Crosses, Genetic; Female; GTP-Binding Protein alpha Subunit, Gi2; GTP-Binding Protein alpha Subunits, Gi-Go - physiology; Intracellular Signaling Peptides and Proteins; Kv1.1 Potassium Channel; Life Sciences; Lysophospholipids - pharmacology; Male; Mice; Mice, Inbred C57BL; Mice, Knockout; Molecular Sequence Data; Nerve Tissue Proteins - deficiency; Nerve Tissue Proteins - genetics; Nerve Tissue Proteins - metabolism; Nerve Tissue Proteins - physiology; Neurons and Cognition; Oligodendroglia - drug effects; Oligodendroglia - metabolism; Oligodendroglia - ultrastructure; Phosphorylation; Potassium Channels, Voltage-Gated - analysis; Protein Processing, Post-Translational; Protein-Serine-Threonine Kinases - metabolism; Protein-Serine-Threonine Kinases - physiology; Proto-Oncogene Proteins - physiology; Proto-Oncogene Proteins c-akt; Rats; Rats, Wistar; Receptors, Lysosphingolipid - deficiency; Receptors, Lysosphingolipid - genetics; Receptors, Lysosphingolipid - physiology; rho-Associated Kinases; RNA, Messenger - analysis; RNA, Small Interfering - pharmacology; Signal Transduction - drug effects; Signal Transduction - physiology; Sphingosine - analogs & derivatives; Sphingosine - pharmacology
• ISSN: 0270-6474; 1529-2401
• DOI: 10.1523/JNEUROSCI.4645-04.2005

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.