Tau protein binds to pericentromeric DNA: a putative role for nuclear tau in nucleolar organization.
The microtubule-associated tau protein participates in the organization and integrity of the neuronal cytoskeleton. A nuclear form of tau has been described in neuronal and non-neuronal cells, which displays a nucleolar localization during interphase but is associated with nucleolar-organizing regions in mitotic cells. In the present study, based on immunofluorescence, immuno-FISH and confocal microscopy, we show that nuclear tau is mainly present at the internal periphery of nucleoli, partially colocalizing with the nucleolar protein nucleolin and human AT-rich alpha-satellite DNA sequences organized as constitutive heterochromatin. By using gel retardation, we demonstrate that tau not only colocalizes with, but also specifically binds to, AT-rich satellite DNA sequences apparently through the recognition of AT-rich DNA stretches. Here we propose a functional role for nuclear tau in relation to the nucleolar organization and/or heterochromatinization of a portion of RNA genes. Since nuclear tau has also been found in neurons from patients with Alzheimer's disease (AD), aberrant nuclear tau could affect the nucleolar organization during the course of AD. We discuss nucleolar tau associated with AT-rich alpha-satellite DNA sequences as a potential molecular link between trisomy 21 and AD.
Sjöberg
Marcela K
MK
Laboratory of Cellular, Molecular Biology and Neurosciences, Millennium Institute for Advanced Studies in Cell Biology and Biotechnology (CBB), Faculty of Sciences, University of Chile, Las Encinas 3370, Nuñoa, Santiago, Chile. cbb@uchile.cl
Shestakova
Elena
E
Mansuroglu
Zeyni
Z
Maccioni
Ricardo B
RB
Bonnefoy
Eliette
E
D000818:Animals; D002466:Cell Nucleolus / Q000378:metabolism*; D004276:DNA, Satellite / Q000378:metabolism*; D024202:Electrophoretic Mobility Shift Assay; D005347:Fibroblasts / Q000378:metabolism; D006367:HeLa Cells; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D008214:Lymphocytes / Q000378:metabolism; D051379:Mice; D018613:Microscopy, Confocal; D011485:Protein Binding; D016875:tau Proteins / Q000378:metabolism*
D004276:DNA, Satellite; D016875:tau Proteins