title: 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.
authors.affiliation: Department of Neuropathology, Neurological Institute Carlo Besta, Milano, Italy. grossi@istituto-besta.it
authors.forename: Giacomina
authors.initials: G
authors.lastname: Rossi
authors.forename: Leda
authors.initials: L
authors.lastname: Dalprà
authors.forename: Francesca
authors.initials: F
authors.lastname: Crosti
authors.forename: Sara
authors.initials: S
authors.lastname: Lissoni
authors.forename: Francesca L
authors.initials: FL
authors.lastname: Sciacca
authors.forename: Marcella
authors.initials: M
authors.lastname: Catania
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Di Fede
authors.forename: Michela
authors.initials: M
authors.lastname: Mangieri
authors.forename: Giorgio
authors.initials: G
authors.lastname: Giaccone
authors.forename: Danilo
authors.initials: D
authors.lastname: Croci
authors.forename: Fabrizio
authors.initials: F
authors.lastname: Tagliavini
mesh_terms: D002467:Cell Nucleus / Q000737:chemistry; D002478:Cells, Cultured; D002843:Chromatin / Q000648:ultrastructure; D043171:Chromosomal Instability; D002869:Chromosome Aberrations; D002877:Chromosomes, Human / Q000737:chemistry; D003704:Dementia / Q000235:genetics*; D005347:Fibroblasts / Q000737:chemistry; D006801:Humans; D008870:Microtubules / Q000737:chemistry; D008875:Middle Aged; D008938:Mitosis; D009154:Mutation; D016875:tau Proteins / Q000032:analysis / Q000235:genetics / Q000502:physiology*
chemical_list: D002843:Chromatin; D016875:tau Proteins