title: Expression of Tau Produces Aberrant Plasma Membrane Blebbing in Glial Cells Through RhoA-ROCK-Dependent F-Actin Remodeling.
abstract: 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.
authors.affiliation: Department of Cell Biology, Center of Research and Advanced Studies of the National Polytechnic Institute (CINVESTAV), Mexico City, Mexico.
authors.forename: Francisco M
authors.initials: FM
authors.lastname: Torres-Cruz
authors.affiliation: Department of Cell Biology, Center of Research and Advanced Studies of the National Polytechnic Institute (CINVESTAV), Mexico City, Mexico.
authors.forename: Fanny
authors.initials: F
authors.lastname: Rodríguez-Cruz
authors.affiliation: Department of Cell Biology, Center of Research and Advanced Studies of the National Polytechnic Institute (CINVESTAV), Mexico City, Mexico.
authors.forename: Jaime
authors.initials: J
authors.lastname: Escobar-Herrera
authors.affiliation: Department of Cell Biology, Center of Research and Advanced Studies of the National Polytechnic Institute (CINVESTAV), Mexico City, Mexico.
authors.forename: Norma
authors.initials: N
authors.lastname: Barragán-Andrade
authors.affiliation: División de Ciencias e Ingenierías, Universidad de Guanajuato, Guanajuato, Mexico.
authors.forename: Gustavo
authors.initials: G
authors.lastname: Basurto-Islas
authors.affiliation: National Institute of Mental Health, Klecany, Czech Republic.
authors.forename: Daniela
authors.initials: D
authors.lastname: Ripova
authors.affiliation: Centro de Biología Molecular Severo Ochoa (CSIC-UAM) Universidad Autónoma de Madrid, Spain.
authors.forename: Jesús
authors.initials: J
authors.lastname: Ávila
authors.affiliation: Department of Cell Biology, Center of Research and Advanced Studies of the National Polytechnic Institute (CINVESTAV), Mexico City, Mexico.
authors.forename: Francisco
authors.initials: F
authors.lastname: Garcia-Sierra
mesh_terms: D000199:Actins / Q000187:drug effects / Q000378:metabolism*; D000818:Animals; D015153:Blotting, Western; D002460:Cell Line; D002462:Cell Membrane / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology; D003593:Cytoplasm / Q000378:metabolism; D004586:Electrophoresis; D005455:Fluorescent Antibody Technique; D049452:Green Fluorescent Proteins / Q000235:genetics / Q000378:metabolism; D020662:Guanine Nucleotide Exchange Factors / Q000378:metabolism; D020287:In Situ Nick-End Labeling; D018613:Microscopy, Confocal; D009457:Neuroglia / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology; D051381:Rats; D015398:Signal Transduction / Q000187:drug effects; D014162:Transfection; D014404:Tubulin / Q000378:metabolism; D054460:rho-Associated Kinases / Q000378:metabolism*; D020742:rhoA GTP-Binding Protein / Q000378:metabolism*; D016875:tau Proteins / Q000235:genetics / Q000378:metabolism*
chemical_list: D000199:Actins; D020662:Guanine Nucleotide Exchange Factors; D014404:Tubulin; D016875:tau Proteins; D049452:Green Fluorescent Proteins; D054460:rho-Associated Kinases; D020742:rhoA GTP-Binding Protein
keywords: F-Actin remodeling; Rho associated protein kinase; RhoGTPases; Tau; glial degeneration; membrane blebbing; tauopathies