Downregulation of the microtubule associated protein T au impairs process outgrowth and myelin basic protein m RNA 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. GLIA 2015;63:1621–1635
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In oligodendrocytes, tau plays a role in process outgrowth and myelination.
“In oligodendrocytes, tau plays a role in process outgrowth and myelination [133, 136–138], however, it remains unclear at this point whether tau regulates physiological functions of astrocytes.”
From Molecular and cellular mechanisms underlying the pathogenesis of Alzheimer’s disease (2020) · cites this paper as [137]
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- Authors
- Seiberlich, V., Bauer, N. G., Schwarz, L., Ffrench‐Constant, C., Goldbaum, O., & Richter‐Landsberg, C.
- Affiliations
- Carl von Ossietzky Universität Oldenburg (DE)
- MRC Centre for Regenerative Medicine (GB)
- Corresponding author
- Richter‐Landsberg, Christiane
- Venue
- Glia
- Publisher
- Wiley
- Published
- 2015-04-04
- Volume
- 63
- Issue
- 9
- Pages
- 1621-1635
- ISSN
- 0894-1491 (ISSN-L)
- 1098-1136
- OpenAlex
- W2114832016
- Cited by
- 84
- References
- 61
- Citations by year
- 2026: 5 · 2025: 7 · 2024: 6 · 2023: 7 · 2022: 10 · 2021: 8 · 2020: 9 · 2019: 7 · 2018: 7 · 2017: 8 · 2016: 3 · 2015: 7
- FWCI
- 3.37
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Glia (publishedVersion)
- PubMed (publishedVersion)
- UEA Digital Repository (University of East Anglia) (submittedVersion)
- Funders
- Deutsche Forschungsgemeinschaft (DFG RI 384/16-2)
- Topics
- Life Sciences › Neuroscience › Developmental Neuroscience › Neurogenesis and neuroplasticity mechanisms
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Microtubule and mitosis dynamics
- Health Sciences › Medicine › Physiology › Alzheimer's disease research and treatments
- Keywords
- tau protein, microtubule-associated proteins, oligodendrocytes, myelin basic protein, mRNA transport, RNA granules, microtubules, oligodendrocyte differentiation, NG2 proteoglycan, myelination, siRNA knockdown, oligodendrocyte precursor cells, dorsal root ganglion neurons
- MeSH terms
- Animals, Brain, Cell Line, Cells, Cultured, Myelin Basic Protein, Ganglia, Spinal, Humans, Microtubules, Myelin Sheath, Neurons, Oligodendroglia, RNA, Messenger, Tubulin, Down-Regulation, tau Proteins, Rats, Wistar, Coculture Techniques, RNA Transport, Proto-Oncogene Proteins c-fyn
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