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Research Article |
CNRS — UPR 2228, Régulation de la Transcription et Maladies Génétiques, Université René Descartes, 45 rue des Saints-Pères, 75270 Paris Cedex 06, France
* Author for correspondence (e-mail: djian{at}biomedicale.univ-paris5.fr )
Accepted 21 November 2001
Huntington's disease results from an expansion of a series of glutamine
repeats in the protein huntingtin. We have discovered from immunopurification
studies that huntingtin combines specifically with the ß subunit of
tubulin. This binding explains why huntingtin can be shown on assembled
microtubules by electron microscopy. Immunostaining shows that most of the
huntingtin in the cytoplasm is associated with microtubules. Huntingtin is
particularly abundant in the perinuclear region, where it is also associated
with microtubules and in the centrosomal region, where it co-localizes with
-tubulin. In Huntington's disease, inclusions are often nuclear or
perinuclear. Since the perinuclear concentration of huntingtin does not depend
on the number of its glutamine repeats, we propose that inclusions are found
in perinuclear and intranuclear locations because the ß-tubulin binding
property of huntingtin brings it to the perinuclear region, from which it
readily gains access to the nucleus. The mutational glutamine expansion then
promotes insolubility and results in an inclusion.
Key words: Polyglutamine, Huntington's disease, Inclusions, Centrosomes, Cytoskeleton, Perikaryon
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