Expression of Tau produces aberrant plasma membrane blebbing in glial cells through RhoA-ROCK-dependent F-Actin remodeling

Result code in IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F00023752%3A_____%2F16%3A43915143" target="_blank" >RIV/00023752:_____/16:43915143 - isvavai.cz</a>

Result on the web

<a href="http://content.iospress.com/articles/journal-of-alzheimers-disease/jad150396" target="_blank" >http://content.iospress.com/articles/journal-of-alzheimers-disease/jad150396</a>

DOI - Digital Object Identifier

<a href="http://dx.doi.org/10.3233/JAD-150396" target="_blank" >10.3233/JAD-150396</a>

Result language

angličtina

Original language name

Expression of Tau produces aberrant plasma membrane blebbing in glial cells through RhoA-ROCK-dependent F-Actin remodeling

Original language description

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 fulllength 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 posttransfection, abnormal microtubule bundling was observed in the majority of the cells, which expressed either Tau441 or Tau421. Moreover, both variants of Tau produced extensivePMblebbing 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 newmechanism 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.

Czech name

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Czech description

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Type

J_x - Unclassified - Peer-reviewed scientific article (Jimp, Jsc and Jost)

CEP classification

FH - Neurology, neuro-surgery, nuero-sciences

OECD FORD branch

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Project

Result was created during the realization of more than one project. More information in the Projects tab.

Continuities

P - Projekt vyzkumu a vyvoje financovany z verejnych zdroju (s odkazem do CEP)

Publication year

2016

Confidentiality

S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů

Name of the periodical

Journal of Alzheimer's Disease

ISSN

1387-2877

e-ISSN

—

Volume of the periodical

52

Issue of the periodical within the volume

2

Country of publishing house

NL - THE KINGDOM OF THE NETHERLANDS

Number of pages

20

Pages from-to

463-482

UT code for WoS article

000376838700007

EID of the result in the Scopus database

2-s2.0-84971265486