title: Translational control of myelin basic protein expression by ERK2 MAP kinase regulates timely remyelination in the adult brain.
abstract: Successful myelin repair in the adult CNS requires the robust and timely production of myelin proteins to generate new myelin sheaths. The underlying regulatory mechanisms and complex molecular basis of myelin regeneration, however, remain poorly understood. Here, we investigate the role of ERK MAP kinase signaling in this process. Conditional deletion of Erk2 from cells of the oligodendrocyte lineage resulted in delayed remyelination following demyelinating injury to the adult mouse corpus callosum. The delayed repair occurred as a result of a specific deficit in the translation of the major myelin protein, MBP. In the absence of ERK2, activation of the ribosomal protein S6 kinase (p70S6K) and its downstream target, ribosomal protein S6 (S6RP), was impaired at a critical time when premyelinating oligodendrocytes were transitioning to mature cells capable of generating new myelin sheaths. Thus, we have described an important link between the ERK MAP kinase signaling cascade and the translational machinery specifically in remyelinating oligodendrocytes in vivo. These results suggest an important role for ERK2 in the translational control of MBP, a myelin protein that appears critical for ensuring the timely generation of new myelin sheaths following demyelinating injury in the adult CNS.
authors.affiliation: Department of Pediatrics, Division of Neurology, University of Pittsburgh, Pittsburgh, Pennsylvania 15224.
authors.forename: Kelly
authors.initials: K
authors.lastname: Michel
authors.affiliation: Department of Pediatrics, Division of Neurology, University of Pittsburgh, Pittsburgh, Pennsylvania 15224.
authors.forename: Tianna
authors.initials: T
authors.lastname: Zhao
authors.affiliation: Department of Pediatrics, Division of Neurology, University of Pittsburgh, Pittsburgh, Pennsylvania 15224.
authors.forename: Molly
authors.initials: M
authors.lastname: Karl
authors.affiliation: Department of Pediatrics, Division of Neurology, University of Pittsburgh, Pittsburgh, Pennsylvania 15224.
authors.forename: Katherine
authors.initials: K
authors.lastname: Lewis
authors.affiliation: Department of Pediatrics, Division of Neurology, University of Pittsburgh, Pittsburgh, Pennsylvania 15224 sharyl.fyffemaricich@chp.edu.
authors.forename: Sharyl L
authors.initials: SL
authors.lastname: Fyffe-Maricich
mesh_terms: D000818:Animals; D003337:Corpus Callosum / Q000166:cytology / Q000254:growth & development / Q000378:metabolism*; D051379:Mice; D008810:Mice, Inbred C57BL; D019950:Mitogen-Activated Protein Kinase 1 / Q000235:genetics / Q000378:metabolism*; D004676:Myelin Basic Protein / Q000235:genetics / Q000378:metabolism*; D009186:Myelin Sheath / Q000378:metabolism*; D038601:Ribosomal Protein S6 / Q000378:metabolism; D038762:Ribosomal Protein S6 Kinases, 70-kDa / Q000378:metabolism; D015398:Signal Transduction
chemical_list: D004676:Myelin Basic Protein; D038601:Ribosomal Protein S6; D038762:Ribosomal Protein S6 Kinases, 70-kDa; C535148:Mapk1 protein, mouse; D019950:Mitogen-Activated Protein Kinase 1
keywords: ERK2 MAP kinase; demyelination; myelin; oligodendrocyte; remyelination