title: Translation of myelin basic protein mRNA in oligodendrocytes is regulated by integrin activation and hnRNP-K.
abstract: Myelination in the central nervous system provides a unique example of how cells establish asymmetry. The myelinating cell, the oligodendrocyte, extends processes to and wraps multiple axons of different diameter, keeping the number of wraps proportional to the axon diameter. Local regulation of protein synthesis represents one mechanism used to control the different requirements for myelin sheath at each axo-glia interaction. Prior work has established that β1-integrins are involved in the axoglial interactions that initiate myelination. Here, we show that integrin activation regulates translation of a key sheath protein, myelin basic protein (MBP), by reversing the inhibitory effect of the mRNA 3'UTR. During oligodendrocyte differentiation and myelination α6β1-integrin interacts with hnRNP-K, an mRNA-binding protein, which binds to MBP mRNA and translocates from the nucleus to the myelin sheath. Furthermore, knockdown of hnRNP-K inhibits MBP protein synthesis during myelination. Together, these results identify a novel pathway by which axoglial adhesion molecules coordinate MBP synthesis with myelin sheath formation.
authors.affiliation: MRC Centre for Regenerative Medicine and MS Society Translational Research Centre, Centre for Inflammation Research, The Queen's Medical Research Institute, University of Edinburgh, Edinburgh EH16 4TJ, Scotland, UK. ll@mb.au.dk
authors.forename: Lisbeth S
authors.initials: LS
authors.lastname: Laursen
authors.forename: Colin W
authors.initials: CW
authors.lastname: Chan
authors.forename: Charles
authors.initials: C
authors.lastname: Ffrench-Constant
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D001692:Biological Transport; D002454:Cell Differentiation; D034641:Heterogeneous-Nuclear Ribonucleoprotein K / Q000032:analysis / Q000235:genetics / Q000502:physiology*; D006801:Humans; D039121:Integrin alpha6beta1 / Q000378:metabolism; D019012:Integrin beta1 / Q000378:metabolism / Q000502:physiology*; D008969:Molecular Sequence Data; D004676:Myelin Basic Protein / Q000235:genetics*; D009186:Myelin Sheath / Q000378:metabolism; D009836:Oligodendroglia / Q000378:metabolism*; D014176:Protein Biosynthesis / Q000502:physiology*; D012333:RNA, Messenger / Q000378:metabolism*; D051381:Rats; D016415:Sequence Alignment; D015398:Signal Transduction; D014157:Transcription Factors / Q000235:genetics*
chemical_list: D034641:Heterogeneous-Nuclear Ribonucleoprotein K; D039121:Integrin alpha6beta1; D019012:Integrin beta1; C436006:Mbp protein, rat; D004676:Myelin Basic Protein; D012333:RNA, Messenger; D014157:Transcription Factors