Non-expanded polyglutamine proteins in intranuclear inclusions of hereditary ataxias - triple-labeling immunofluorescence study

Neuronal intranuclear inclusions (NIIs) found in CAG/polyglutamine-expansio n disorders contain both expanded polyglutamine and the gene product withou t the CAG repeat. The gene product containing expanded polyglutamine has, t herefore, been considered to be a major component of NIIs. In this immunohi stochemical study, we showed recruitment of ataxin-2, ataxin-3 and TATA box binding protein (TBP) into NIIs of the pontine neurons of spinocerebellar ataxia type (SCA) 1, SCA2, SCA3 and dentatorubral-pallidoluysian atrophy br ains. Triple-labeling immunofluorescence demonstrated colocalization of ata xin-2 and ataxin-3 in NIIs containing expanded polyglutamine, irrespective of the disease examined. These in vivo findings indicate that polyglutamine proteins recruited into NIIs are not restricted to their expanded form. Am ong these proteins, recruitment of ataxin-2 was least frequent in every cas e examined, suggesting that the rate of recruitment partly depends on the p rotein transported into NIIs. Because other proteins lacking polyglutamine motif were not detected in NIIs, it is suggested that the presence of polyg lutamine is a prerequisite for these proteins to be recruited into nucleus and to form NIIs. Interaction between expanded and non-expanded polyglutami ne may play roles during these processes.