Expression of Tau Produces Aberrant Plasma Membrane Blebbing in Glial Cells Through RhoA-ROCK-Dependent F-Actin Remodeling
Jazyk angličtina Země Spojené státy americké Médium print
Typ dokumentu časopisecké články, práce podpořená grantem
PubMed
27003208
DOI
10.3233/jad-150396
PII: JAD150396
Knihovny.cz E-zdroje
- Klíčová slova
- F-Actin remodeling, Rho associated protein kinase, RhoGTPases, Tau, glial degeneration, membrane blebbing, tauopathies,
- MeSH
- aktiny účinky léků metabolismus MeSH
- buněčná membrána účinky léků metabolismus patologie MeSH
- buněčné linie MeSH
- cytoplazma metabolismus MeSH
- elektroforéza MeSH
- fluorescenční protilátková technika MeSH
- kinázy asociované s Rho metabolismus MeSH
- koncové značení zlomů DNA in situ MeSH
- konfokální mikroskopie MeSH
- krysa rodu Rattus MeSH
- neuroglie účinky léků metabolismus patologie MeSH
- proteiny tau genetika metabolismus MeSH
- rhoA protein vázající GTP metabolismus MeSH
- signální transdukce účinky léků MeSH
- transfekce MeSH
- tubulin metabolismus MeSH
- výměnné faktory guaninnukleotidů metabolismus MeSH
- western blotting MeSH
- zelené fluorescenční proteiny genetika metabolismus MeSH
- zvířata MeSH
- Check Tag
- krysa rodu Rattus MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- Názvy látek
- aktiny MeSH
- kinázy asociované s Rho MeSH
- proteiny tau MeSH
- rhoA protein vázající GTP MeSH
- tubulin MeSH
- výměnné faktory guaninnukleotidů MeSH
- zelené fluorescenční proteiny 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
Citace poskytuje Crossref.org