Focal distortion of the nuclear envelope by huntingtin aggregates revealed by lamin immunostaining

NEUROSCIENCE LETTERS

卷:447

Article

Chapple, J. Paul¹  Bros-Facer, Virginie¹  Butler, Rachel¹  Gallo, Jean-Marc¹ 

[1] Kings Coll London, MRC Ctr Neurodegenerat Res, Inst Psychiat, Dept Clin Neurosci, London SE5 8AF, England

关键词: Polyglutamine;    Huntingtin;    Aggregation;    Lamin;    Nuclear envelope;   

DOI  :  10.1016/j.neulet.2008.09.075

来源: Elsevier

【 摘 要 】

Huntington's disease is an autosomal dominant neurodegenerative disorder caused by the expansion of a polyglutamine repeat tract in the huntingtin protein. Polyglutamine-expanded huntingtin forms intranuclear as well as perinuclear inclusion bodies. Perinuclear aggregates formed by polyglutamine-expanded proteins are associated with a characteristic indentation of the nuclear envelope. We examined the nuclear envelope in cells containing huntingtin aggregates using immunostaining for lamin B1, a major component of the nuclear lamina. Laser confocal microscopy analysis revealed that huntingtin aggregates in a juxtanuclear position were associated with a clear focal distortion in the nuclear envelope in cells transfected with polyglutamine-expanded huntingtin. Lamin B1 distribution was not altered by aggregates of polyglutamine-expanded ataxin-1, that are exclusively intranuclear. Thus lamin immunocytochemistry demonstrates clearly the depression of the nuclear envelope resulting from the formation of perinuclear aggregates by polyglutamine-expanded huntingtin. Lamin immunocytochemistry would be of value to monitor the state of the nuclear envelope in experimental paradigms aimed at establishing the significance of perinuclear aggregates of pathogenic proteins. (C) 2008 Elsevier Ireland Ltd. All rights reserved.

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