A new function of microtubule-associated protein tau: Involvement in chromosome stability

Abstract

Tau is a microtubule-associated protein that promotes assembly and stabilization of cytoskeleton microtubules. It is mostly expressed in neuronal and glial cells but it is also present in non-neural cells such as fibroblasts and lymphocytes. An altered tau produces cytoskeleton pathology resulting in neurodegenerative diseases such as Alzheimer's disease and tauopathies. Tau has been suggested to be a multifunctional protein, due to its localization in different cellular compartments. However its further functions are still unclear. We analyzed the distribution of tau in human skin fibroblasts showing its localization in the nucleus and along mitotic chromosomes. Then, we investigated if an altered tau, such as the P301L mutated protein associated with frontotemporal dementia, could produce nuclear pathology. We found that patients carrying the mutation consistently had several chromosome aberrations in their fibroblasts and lymphocytes: chromosome and chromatid breakages or gaps, aneuploidies, translocations, in addition to chromatin bridges and decondensed chromosomes. Our findings argue for a role of tau in chromosome stability by means of its interaction with both microtubules and chromatin.

Delta-Secretase Phosphorylation by SRPK2 Enhances Its Enzymatic Activity, Provoking Pathogenesis in Alzheimer’s Disease

“…The aneuploid and hyperploid neurons that arise in AD are particularly prone to degeneration and could account for 90% of the neuronal loss that characterizes late-stage AD (Arendt et al, 2010). Individuals with Tau P301L mutation, which is associated with frontotemporal dementia, have several chromosome aberrations, such as aneuploidies in their fibroblasts and lymphocytes (Rossi et al, 2008). Consequently, increased level of aneuploidy in splenic lymphocytes of tauopathy transgenic mouse models have recently been reported (Rossi et al, 2014).…”

Alzheimer Aβ disrupts the mitotic spindle and directly inhibits mitotic microtubule motors

“…30,55,56 MT motors are particularly critical in neurons, which must transport vesicles, organelles and molecules, including microtubules themselves over great distances. 57 Indeed, some studies have shown axonal transport to be disrupted in cell and animal models of AD.…”

Nuclear Tau, a Key Player in Neuronal DNA Protection

“…However, contradictory in vitro results have shown a protective or deleterious role of Tau in DNA integrity (7)(8)(9). In addition, a recent study reported chromosomal aberrations in fibroblasts and lymphocytes from patients carrying a Tau mutation (10).…”