Forcefully Translated

Science Signaling  15 Mar 2011:
Vol. 4, Issue 164, pp. ec78
DOI: 10.1126/scisignal.4164ec78

A major component of the myelin sheath is myelin basic protein (MBP). mRNAs encoding MBP are transported to and translated at sites where MBP is required. The β1 integrin subunit, which is the receptor for laminin, promotes myelination, and it interacts with an mRNA-binding protein, hnRNP-K, leading Laursen et al. to determine whether integrin-mediated signaling affects the translation of the mRNA encoding MBP. Overexpression of a constitutively active form of β1 integrin (D759R) in cultured oligodendrocytes increased the number of cells forming myelin sheets in the absence of laminin and that were positive for MBP compared to oligodendrocytes expressing wild-type β1 integrin. The 3′UTR of the mRNA encoding MBP interacts with factors that block translation, and the abundance of MBP protein was lower in oligodendrocyte precursor cells transfected with MBP constructs bearing the 3′UTR compared to those transfected with constructs without the 3′UTR. Overexpression of the constitutively active form of β1 integrin increased the abundance of MBP in oligodendrocyte precursors transfected with the MBP construct with the 3′UTR. Biochemical analysis and immunocytochemistry indicated that the association of hnRNP-K with α6β1 integrin was increased in oligodendrocytes cultured on laminin. Furthermore, the association of the mRNA encoding MBP with hnRNP-K was decreased and hnRNP-K was tyrosine phosphorylated in oligodendrocytes cultured on laminin. RNA interference directed against hnRNP-K resulted in reduced abundance of MBP mRNA and protein, counteracted the laminin-induced increase in MBP protein abundance, and altered distribution of MBP-encoding mRNAs. Thus, activation of β1 integrins on oligodendrocytes promotes translation of MBP-encoding mRNAs through hnRNP-K.

L. S. Laursen, C. W. Chan, C. ffrench-Constant, Translation of myelin basic protein mRNA in oligodendrocytes is regulated by integrin activation and hnRNP-K. J. Cell. Biol. 192, 797–811 (2011). [PubMed]