title: Neuron to glia signaling triggers myelin membrane exocytosis from endosomal storage sites.
abstract: During vertebrate brain development, axons are enwrapped by myelin, an insulating membrane produced by oligodendrocytes. Neuron-derived signaling molecules are temporally and spatially required to coordinate oligodendrocyte differentiation. In this study, we show that neurons regulate myelin membrane trafficking in oligodendrocytes. In the absence of neurons, the major myelin membrane protein, the proteolipid protein (PLP), is internalized and stored in late endosomes/lysosomes (LEs/Ls) by a cholesterol-dependent and clathrin-independent endocytosis pathway that requires actin and the RhoA guanosine triphosphatase. Upon maturation, the rate of endocytosis is reduced, and a cAMP-dependent neuronal signal triggers the transport of PLP from LEs/Ls to the plasma membrane. These findings reveal a fundamental and novel role of LEs/Ls in oligodendrocytes: to store and release PLP in a regulated fashion. The release of myelin membrane from LEs/Ls by neuronal signals may represent a mechanism to control myelin membrane growth.
authors.affiliation: Centre for Biochemistry and Molecular Cell Biology, University of Göttingen, 37073 Göttingen, Germany.
authors.forename: Katarina
authors.initials: K
authors.lastname: Trajkovic
authors.forename: Ajit Singh
authors.initials: AS
authors.lastname: Dhaunchak
authors.forename: José T
authors.initials: JT
authors.lastname: Goncalves
authors.forename: Dirk
authors.initials: D
authors.lastname: Wenzel
authors.forename: Anja
authors.initials: A
authors.lastname: Schneider
authors.forename: Gertrude
authors.initials: G
authors.lastname: Bunt
authors.forename: Klaus-Armin
authors.initials: KA
authors.lastname: Nave
authors.forename: Mikael
authors.initials: M
authors.lastname: Simons
mesh_terms: D000255:Adenosine Triphosphate / Q000378:metabolism; D000818:Animals; D001921:Brain / Q000254:growth & development / Q000378:metabolism / Q000648:ultrastructure; D002450:Cell Communication / Q000502:physiology*; D002454:Cell Differentiation / Q000502:physiology; D002478:Cells, Cultured; D018920:Coculture Techniques; D000242:Cyclic AMP / Q000378:metabolism; D004705:Endocytosis / Q000502:physiology; D011992:Endosomes / Q000378:metabolism* / Q000648:ultrastructure; D004734:Energy Metabolism / Q000502:physiology; D005089:Exocytosis / Q000502:physiology*; D051379:Mice; D046529:Microscopy, Electron, Transmission; D018991:Myelin Proteolipid Protein / Q000378:metabolism; D009186:Myelin Sheath / Q000378:metabolism* / Q000648:ultrastructure; D009474:Neurons / Q000378:metabolism* / Q000648:ultrastructure; D009836:Oligodendroglia / Q000378:metabolism* / Q000648:ultrastructure; D021381:Protein Transport / Q000502:physiology; D015398:Signal Transduction / Q000502:physiology; D020742:rhoA GTP-Binding Protein / Q000378:metabolism
chemical_list: D018991:Myelin Proteolipid Protein; D000255:Adenosine Triphosphate; D000242:Cyclic AMP; D020742:rhoA GTP-Binding Protein