Expression of Tau Produces Aberrant Plasma Membrane Blebbing in Glial Cells Through RhoA-ROCK-Dependent F-Actin Remodeling
Language English Country United States Media print
Document type Journal Article, Research Support, Non-U.S. Gov't
PubMed
27003208
DOI
10.3233/jad-150396
PII: JAD150396
Knihovny.cz E-resources
- Keywords
- F-Actin remodeling, Rho associated protein kinase, RhoGTPases, Tau, glial degeneration, membrane blebbing, tauopathies,
- MeSH
- Actins drug effects metabolism MeSH
- Cell Membrane drug effects metabolism pathology MeSH
- Cell Line MeSH
- Cytoplasm metabolism MeSH
- Electrophoresis MeSH
- Fluorescent Antibody Technique MeSH
- rho-Associated Kinases metabolism MeSH
- In Situ Nick-End Labeling MeSH
- Microscopy, Confocal MeSH
- Rats MeSH
- Neuroglia drug effects metabolism pathology MeSH
- tau Proteins genetics metabolism MeSH
- rhoA GTP-Binding Protein metabolism MeSH
- Signal Transduction drug effects MeSH
- Transfection MeSH
- Tubulin metabolism MeSH
- Guanine Nucleotide Exchange Factors metabolism MeSH
- Blotting, Western MeSH
- Green Fluorescent Proteins genetics metabolism MeSH
- Animals MeSH
- Check Tag
- Rats MeSH
- Animals MeSH
- Publication type
- Journal Article MeSH
- Research Support, Non-U.S. Gov't MeSH
- Names of Substances
- Actins MeSH
- rho-Associated Kinases MeSH
- tau Proteins MeSH
- rhoA GTP-Binding Protein MeSH
- Tubulin MeSH
- Guanine Nucleotide Exchange Factors MeSH
- Green Fluorescent Proteins MeSH
Abnormal aggregation of Tau in glial cells has been reported in Alzheimer's disease (AD) and other tauopathies; however, the pathological significance of these aggregates remains unsolved to date. In this study, we evaluated whether full-length Tau (Tau441) and its aspartic acid421-truncated Tau variant (Tau421) produce alterations in the normal organization of the cytoskeleton and plasma membrane (PM) when transiently expressed in cultured C6-glial cells. Forty-eight hours post-transfection, abnormal microtubule bundling was observed in the majority of the cells, which expressed either Tau441 or Tau421. Moreover, both variants of Tau produced extensive PM blebbing associated with cortical redistribution of filamentous actin (F-Actin). These effects were reverted when Tau-expressing cells were incubated with drugs that depolymerize F-Actin. In addition, when glial cells showing Tau-induced PM blebbing were incubated with inhibitors of the Rho-associated protein kinase (ROCK) signaling pathway, both formation of abnormal PM blebs and F-Actin remodeling were avoided. All of these effects were initiated upstream by abnormal Tau-induced microtubule bundling, which may release the microtubule-bound guanine nucleotide exchange factor-H1 (GEF-H1) into the cytoplasm in order to activate its major effector RhoA-GTPase. These results may represent a new mechanism of Tau toxicity in which Tau-induced microtubule bundling produces activation of the Rho-GTPase-ROCK pathway that in turn mediates the remodeling of cortical Actin and PM blebbing. In AD and other tauopathies, these Tau-induced abnormalities may occur and contribute to the impairment of glial activity.
Centro de Biología Molecular Severo Ochoa Universidad Autónoma de Madrid Spain
División de Ciencias e Ingenierías Universidad de Guanajuato Guanajuato Mexico
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