Translational Control of Myelin Basic Protein Expression by ERK2 MAP Kinase Regulates Timely Remyelination in the Adult Brain

• DOI: 10.1523/jneurosci.4380-14.2015
• Publication Date: 2015-05-20T16:45:10Z
• Authors: Kelly Michel; Tianna Zhao; Molly Karl; Katherine Lewis; Sharyl L. Fyffe-M...
• Keywords: Mice, Inbred C57BL; Mitogen-Activated Protein Kinase 1; 0301 basic medicine; Mice; Ribosomal Protein S6; 03 medical and health sciences; Animals; Ribosomal Protein S6 Kinases, 70-kDa; Myelin Basic Protein; Myelin Sheath; Corpus Callosum; Signal Transduction

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 ofErk2from 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 oligodendrocytesin 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.