title: Downregulation of the microtubule associated protein tau impairs process outgrowth and myelin basic protein mRNA transport in oligodendrocytes.
abstract: Oligodendrocytes, the myelin forming cells of the CNS, are characterized by their numerous membranous extensions, which enwrap neuronal axons and form myelin sheaths. During differentiation oligodendrocytes pass different morphological stages, downregulate the expression of the proteoglycan NG2, and acquire major myelin specific proteins, such as myelin basic proteins (MBP) and proteolipid protein. MBP mRNA is transported in RNA granules along the microtubules (MTs) to the periphery and translated locally. MTs participate in the elaboration and stabilization of the myelin forming extensions and are essential for cellular sorting processes. Their dynamic properties are regulated by microtubule associated proteins (MAPs). The MAP tau is present in oligodendrocytes and involved in the regulation and stabilization of the MT network. To further elucidate the functional significance of tau in oligodendrocytes, we have downregulated tau by siRNA technology and studied the effects on cell differentiation and neuron-glia contact formation. The data show that tau knockdown impairs process outgrowth and leads to a decrease in MBP expression. Furthermore, MBP mRNA transport to distant cellular extensions is impaired and cells remain in the NG2 stage. In myelinating cocultures with dorsal root ganglion neurons, oligodendrocyte precursor cells after tau miR RNA lentiviral knockdown develop into NG2 positive cells with very long and thin processes, contacting axons loosely, but fail to form internodes. This demonstrates that tau is important for MBP mRNA transport and involved in process formation. The disturbance of the balance of tau leads to abnormalities in oligodendrocyte differentiation, neuron-glia contact formation and the early myelination process.
authors.affiliation: Department for Neuroscience, Molecular Neurobiology, University of Oldenburg, Oldenburg, Germany.
authors.forename: Veronika
authors.initials: V
authors.lastname: Seiberlich
authors.affiliation: Department for Neuroscience, Molecular Neurobiology, University of Oldenburg, Oldenburg, Germany.|MRC Centre for Regenerative Medicine, The University of Edinburgh, Edinburgh BioQuarter, Edinburgh, United Kingdom.
authors.forename: Nina G
authors.initials: NG
authors.lastname: Bauer
authors.affiliation: Department for Neuroscience, Molecular Neurobiology, University of Oldenburg, Oldenburg, Germany.
authors.forename: Lisa
authors.initials: L
authors.lastname: Schwarz
authors.affiliation: MRC Centre for Regenerative Medicine, The University of Edinburgh, Edinburgh BioQuarter, Edinburgh, United Kingdom.
authors.forename: Charles
authors.initials: C
authors.lastname: Ffrench-Constant
authors.affiliation: Department for Neuroscience, Molecular Neurobiology, University of Oldenburg, Oldenburg, Germany.
authors.forename: Olaf
authors.initials: O
authors.lastname: Goldbaum
authors.affiliation: Department for Neuroscience, Molecular Neurobiology, University of Oldenburg, Oldenburg, Germany.
authors.forename: Christiane
authors.initials: C
authors.lastname: Richter-Landsberg
mesh_terms: D000818:Animals; D001921:Brain / Q000378:metabolism; D002460:Cell Line; D002478:Cells, Cultured; D018920:Coculture Techniques; D015536:Down-Regulation; D005727:Ganglia, Spinal / Q000378:metabolism; D006801:Humans; D008870:Microtubules / Q000378:metabolism; D004676:Myelin Basic Protein / Q000378:metabolism*; D009186:Myelin Sheath / Q000378:metabolism; D009474:Neurons / Q000378:metabolism; D009836:Oligodendroglia / Q000378:metabolism*; D051076:Proto-Oncogene Proteins c-fyn / Q000378:metabolism; D034443:RNA Transport / Q000502:physiology*; D012333:RNA, Messenger / Q000378:metabolism*; D017208:Rats, Wistar; D014404:Tubulin / Q000378:metabolism; D016875:tau Proteins / Q000235:genetics / Q000378:metabolism*
chemical_list: C054369:MAPT protein, human; C489131:Mapt protein, rat; C436006:Mbp protein, rat; D004676:Myelin Basic Protein; D012333:RNA, Messenger; D014404:Tubulin; D016875:tau Proteins; C494961:Fyn protein, rat; D051076:Proto-Oncogene Proteins c-fyn
keywords: Fyn kinase; NG2 cells; microtubule bundling; myelination; neuron-glia interaction; rat brain