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Polyglutamine Expansion Accelerates the Dynamics of Ataxin-1 and Does Not Result in Aggregate Formation
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@MISC{Krol_polyglutamineexpansion,
author = {Hilde A. Krol and Przemek M. Krawczyk and Klazien S. Bosch and Jacob A. Aten and Elly M. Hol and Eric A. Reits},
title = {Polyglutamine Expansion Accelerates the Dynamics of Ataxin-1 and Does Not Result in Aggregate Formation},
year = {}
}
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Abstract
Background. Polyglutamine expansion disorders are caused by an expansion of the polyglutamine (polyQ) tract in the disease related protein, leading to severe neurodegeneration. All polyQ disorders are hallmarked by the presence of intracellular aggregates containing the expanded protein in affected neurons. The polyQ disorder SpinoCerebellar Ataxia 1 (SCA1) is caused by a polyQ-expansion in the ataxin-1 protein, which is thought to lead to nuclear aggregates. Methodology/Principal Findings. Using advanced live cell fluorescence microscopy and a filter retardation assay we show that nuclear accumulations formed by polyQ-expanded ataxin-1 do not resemble aggregates of other polyQ-expanded proteins. Instead of being static, insoluble aggregates, nuclear accumulations formed by the polyQ-expanded ataxin-1 showed enhanced intracellular kinetics as compared to wild-type ataxin-1. During mitosis, ataxin-1 accumulations redistributed equally among daughter cells, in contrast to polyQ aggregates. Interestingly, polyQ expansion did not affect the nuclear-cytoplasmic shuttling of ataxin-1 as proposed before. Conclusions/Significance. These results indicate that polyQ expansion does not necessarily lead to aggregate formation, and that the enhanced kinetics may affect the nuclear function of ataxin-1. The unexpected findings for a polyQ-expanded protein and their consequences for ongoing SCA1 research are discussed.
Keyphrases
polyglutamine expansion aggregate formation polyq-expanded protein nuclear accumulation polyq expansion polyq-expanded ataxin-1 ataxin-1 protein insoluble aggregate nuclear aggregate intracellular aggregate methodology principal finding conclusion significance affected neuron enhanced intracellular kinetics polyglutamine expansion disorder sca1 research polyq disorder enhanced kinetics ataxin-1 accumulation disease related protein filter retardation unexpected finding nuclear function severe neurodegeneration live cell fluorescence microscopy nuclear-cytoplasmic shuttling daughter cell polyq disorder spinocerebellar ataxia
