Ultrastructure of nuclear aggregates formed by expressing an expanded polyglutamine.

Abstract:

:Intranuclear inclusions have been observed in the brains of patients affected with Huntington's disease (HD). Neuro 2A cells that transiently expressed HD exon 1 bearing 74 glutamine repeats linked to the green fluorescent protein (GFP) and the nuclear localization sequence (NLS) contained aggregates in nuclei. The aggregates were purified by fractionation with centrifugation followed by fluorescence-activated cell sorting (FACS). Heat treatment of the aggregate in an SDS sample buffer caused the dense aggregate cores to disappear and generated a basket-like structure composed of fibrils. Biochemical analysis of the aggregates revealed that the HD exon 1-GFP fusion protein was the major component. The heterogeneous nuclear ribonucleoproteins F and H, histones and ubiquitin were found to be associated with the aggregates. Our observations suggest that the N-terminal fragment of huntingtin may organize the skeletal structure of the aggregates and may disturb normal cellular functions by trapping other proteins within the aggregates.

authors

Hazeki N,Tsukamoto T,Yazawa I,Koyama M,Hattori S,Someki I,Iwatsubo T,Nakamura K,Goto J,Kanazawa I

doi

10.1016/S0006-291X(02)00498-9

subject

Has Abstract

pub_date

2002-06-07 00:00:00

pages

429-40

issue

2

eissn

0006-291X

issn

1090-2104

pii

S0006-291X(02)00498-9

journal_volume

294

pub_type

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