Affiliations: [a]
Department of Cell Biology, Center of Research and Advanced Studies of the National Polytechnic Institute (CINVESTAV), Mexico City, Mexico
| [b]
Department of Pharmacology at the Medical School, Autonomous University of Baja California, Mexicali, Mexico
| [c] Division of Science and Engineering, University of Guanajuato, León, Mexico
| [d] Centro de Biología Molecular Severo Ochoa (CSIC-UAM) Universidad Autónoma de Madrid, Madrid, Spain
Correspondence:
[*]
Correspondence to: Francisco García-Sierra, Department of Cell Biology, Center of Research and Advanced Studies of the National Polytechnic Institute (CINVESTAV-IPN), Av. Instituto Politécnico Nacional 2508, CP
07360 Ciudad de México (CDMX), México. Tel.: +52 55 5747 3354; Fax: +52 55 5747 3393;
E-mail: [email protected]. E-mail: [email protected].
Abstract: Abnormal fibrillary aggregation of tau protein is a pathological condition observed in Alzheimer’s disease and other tauopathies; however, the presence and pathological significance of early non-fibrillary aggregates of tau remain under investigation. In cell and animal models expressing normal or modified tau, toxic effects altering the structure and function of several membranous organelles have also been reported in the absence of fibrillary structures; however, how these abnormalities are produced is an issue yet to be addressed. In order to obtain more insights into the mechanisms by which tau may disturb intracellular membranous elements, we transiently overexpressed human full-length tau and several truncated tau variants in cultured neuroblastoma cells. After 48 h of transfection, either full-length or truncated tau forms produced significant fragmentation of the Golgi apparatus (GA) with no changes in cell viability. Noteworthy is that in the majority of cells exhibiting dispersion of the GA, a ring-shaped array of cortical or perinuclear microtubule (Mt) bundles was also generated under the expression of either variant of tau. In contrast, Taxol treatment of non-transfected cells increased the amount of Mt bundles but not sufficiently to produce fragmentation of the GA. Tau-induced ring-shaped Mt bundles appeared to be well-organized and stable structures because they were resistant to Nocodazole post-treatment and displayed a high level of tubulin acetylation. These results further indicate that a mechanical force generated by tau-induced Mt-bundling may be responsible for Golgi fragmentation and that the repeated domain region of tau may be the main promoter of this effect.
