title: Edg8/S1P5: an oligodendroglial receptor with dual function on process retraction and cell survival.
abstract: 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.
authors.affiliation: Biologie des Interactions Neurones/Glie, Institut National de la Santé et de la Recherche Médicale and Université Pierre et Marie Curie, Unité Mixte de Recherche 711, Hôpital de la Salpêtrière, F-75651 Paris, France.
authors.forename: C
authors.initials: C
authors.lastname: Jaillard
authors.forename: S
authors.initials: S
authors.lastname: Harrison
authors.forename: B
authors.initials: B
authors.lastname: Stankoff
authors.forename: M S
authors.initials: MS
authors.lastname: Aigrot
authors.forename: A R
authors.initials: AR
authors.lastname: Calver
authors.forename: G
authors.initials: G
authors.lastname: Duddy
authors.forename: F S
authors.initials: FS
authors.lastname: Walsh
authors.forename: M N
authors.initials: MN
authors.lastname: Pangalos
authors.forename: N
authors.initials: N
authors.lastname: Arimura
authors.forename: K
authors.initials: K
authors.lastname: Kaibuchi
authors.forename: B
authors.initials: B
authors.lastname: Zalc
authors.forename: C
authors.initials: C
authors.lastname: Lubetzki
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D017487:Ankyrins / Q000032:analysis; D001921:Brain / Q000166:cytology / Q000254:growth & development; D001923:Brain Chemistry; D002454:Cell Differentiation; D019070:Cell Lineage; D048430:Cell Shape / Q000187:drug effects; D022081:Cell Surface Extensions / Q000187:drug effects / Q000502:physiology*; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured / Q000187:drug effects / Q000378:metabolism / Q000648:ultrastructure; D003433:Crosses, Genetic; D005260:Female; D051960:GTP-Binding Protein alpha Subunit, Gi2; D019206:GTP-Binding Protein alpha Subunits, Gi-Go / Q000502:physiology; D036341:Intercellular Signaling Peptides and Proteins; D047908:Intracellular Signaling Peptides and Proteins; D051662:Kv1.1 Potassium Channel; D008246:Lysophospholipids / Q000494:pharmacology*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008969:Molecular Sequence Data; D009419:Nerve Tissue Proteins / Q000172:deficiency / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D009836:Oligodendroglia / Q000187:drug effects / Q000378:metabolism* / Q000648:ultrastructure; D010766:Phosphorylation; D024642:Potassium Channels, Voltage-Gated / Q000032:analysis; D011499:Protein Processing, Post-Translational; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism / Q000502:physiology; D011518:Proto-Oncogene Proteins / Q000502:physiology; D051057:Proto-Oncogene Proteins c-akt; D012333:RNA, Messenger / Q000032:analysis; D034741:RNA, Small Interfering / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D049349:Receptors, Lysosphingolipid / Q000172:deficiency / Q000235:genetics / Q000502:physiology*; D015398:Signal Transduction / Q000187:drug effects / Q000502:physiology; D013110:Sphingosine / Q000031:analogs & derivatives* / Q000494:pharmacology; D054460:rho-Associated Kinases
chemical_list: C094681:Ank3 protein, mouse; D017487:Ankyrins; D036341:Intercellular Signaling Peptides and Proteins; D047908:Intracellular Signaling Peptides and Proteins; C496947:Kcna1 protein, mouse; D008246:Lysophospholipids; D009419:Nerve Tissue Proteins; D024642:Potassium Channels, Voltage-Gated; D011518:Proto-Oncogene Proteins; D012333:RNA, Messenger; D034741:RNA, Small Interfering; D049349:Receptors, Lysosphingolipid; C095114:collapsin response mediator protein-2; D051662:Kv1.1 Potassium Channel; C060506:sphingosine 1-phosphate; C494920:Akt1 protein, rat; D017346:Protein Serine-Threonine Kinases; D051057:Proto-Oncogene Proteins c-akt; D054460:rho-Associated Kinases; D051960:GTP-Binding Protein alpha Subunit, Gi2; D019206:GTP-Binding Protein alpha Subunits, Gi-Go; C498016:Gnai2 protein, mouse; C498017:Gnai2 protein, rat; D013110:Sphingosine