Focal distortion of the nuclear envelope by huntingtin aggregates revealed by lamin immunostaining.
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.
MRC Centre for Neurodegeneration Research, King's College London, Department of Clinical Neuroscience, Institute of Psychiatry, De Crespigny Park, London SE5 8AF, United Kingdom.
J Paul
JP
Chapple
Virginie
V
Bros-Facer
Rachel
R
Butler
Jean-Marc
JM
Gallo
D000818:Animals; D000067696:Ataxin-1; D000067528:Ataxins; D016466:CHO Cells / Q000648:ultrastructure; D006224:Cricetinae; D003412:Cricetulus; D005973:Glutamine / Q000378:metabolism; D049452:Green Fluorescent Proteins / Q000235:genetics; D006801:Humans; D000071058:Huntingtin Protein; D002479:Inclusion Bodies / Q000235:genetics / Q000378:metabolism; D034921:Lamin Type B / Q000378:metabolism*; D018613:Microscopy, Confocal / Q000379:methods; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000378:metabolism*; D009685:Nuclear Envelope / Q000235:genetics / Q000378:metabolism*; D009687:Nuclear Proteins / Q000235:genetics / Q000378:metabolism*; D010455:Peptides / Q000235:genetics; D014162:Transfection / Q000379:methods
C000593749:ATXN1 protein, human; D000067696:Ataxin-1; D000067528:Ataxins; C086055:HTT protein, human; D000071058:Huntingtin Protein; D034921:Lamin Type B; D009419:Nerve Tissue Proteins; D009687:Nuclear Proteins; D010455:Peptides; D005973:Glutamine; D049452:Green Fluorescent Proteins; C097188:polyglutamine