Activation of oligodendroglial Fyn kinase enhances translation of mRNAs transported in hnRNP A2-dependent RNA granules.
Central nervous system myelination requires the synthesis of large amounts of myelin basic protein (MBP) at the axon-glia contact site. MBP messenger RNA (mRNA) is transported in RNA granules to oligodendroglial processes in a translationally silenced state. This process is regulated by the trans-acting factor heterogeneous nuclear ribonucleoprotein (hnRNP) A2 binding to the cis-acting A2 response element (A2RE). Release of this repression of MBP mRNA translation is thus essential for myelination. Mice deficient in the Src family tyrosine kinase Fyn are hypomyelinated and contain reduced levels of MBP. Here, we identify hnRNP A2 as a target of activated Fyn in oligodendrocytes. We show that active Fyn phosphorylates hnRNP A2 and stimulates translation of an MBP A2RE-containing reporter construct. Neuronal adhesion molecule L1 binding to oligodendrocytes results in Fyn activation, which leads to an increase in hnRNP A2 phosphorylation. These results suggest that Fyn kinase activation results in the localized translation of MBP mRNA at sites of axon-glia contact and myelin deposition.
White
Robin
R
Molecular Cell Biology, Department of Biology, Johannes Gutenberg University of Mainz, 55128 Mainz, Germany.
Gonsior
Constantin
C
Krämer-Albers
Eva-Maria
EM
Stöhr
Nadine
N
Hüttelmaier
Stefan
S
Trotter
Jacqueline
J
D000818:Animals; D015816:Cell Adhesion Molecules, Neuronal / Q000378:metabolism; D002460:Cell Line; D058966:Contactins; D003594:Cytoplasmic Granules / Q000378:metabolism*; D004789:Enzyme Activation; D017930:Genes, Reporter; D034481:Heterogeneous-Nuclear Ribonucleoprotein Group A-B / Q000378:metabolism*; D008156:Luciferases / Q000378:metabolism; D051379:Mice; D019006:Neural Cell Adhesion Molecules / Q000378:metabolism; D009836:Oligodendroglia / Q000201:enzymology*; D010766:Phosphorylation; D011485:Protein Binding; D014176:Protein Biosynthesis; D051076:Proto-Oncogene Proteins c-fyn / Q000378:metabolism*; D034443:RNA Transport; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D011993:Recombinant Fusion Proteins / Q000378:metabolism; D020218:Response Elements / Q000235:genetics
D015816:Cell Adhesion Molecules, Neuronal; D058966:Contactins; D034481:Heterogeneous-Nuclear Ribonucleoprotein Group A-B; D019006:Neural Cell Adhesion Molecules; D012333:RNA, Messenger; D011993:Recombinant Fusion Proteins; C439768:hnRNP A2; D008156:Luciferases; D051076:Proto-Oncogene Proteins c-fyn