Polyglutamine expansion accelerates the dynamics of ataxin-1 and does not result in aggregate formation.

<h4>Background</h4>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 p...

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Autores principales:	Hilde A Krol, Przemek M Krawczyk, Klazien S Bosch, Jacob A Aten, Elly M Hol, Eric A Reits
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2008
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/331efd107d164418ade7f1f56bb701eb
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spelling	oai:doaj.org-article:331efd107d164418ade7f1f56bb701eb2021-11-25T06:13:33ZPolyglutamine expansion accelerates the dynamics of ataxin-1 and does not result in aggregate formation.1932-620310.1371/journal.pone.0001503https://doaj.org/article/331efd107d164418ade7f1f56bb701eb2008-01-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/18231590/pdf/?tool=EBIhttps://doaj.org/toc/1932-6203<h4>Background</h4>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.<h4>Methodology/principal findings</h4>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.<h4>Conclusions/significance</h4>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.Hilde A KrolPrzemek M KrawczykKlazien S BoschJacob A AtenElly M HolEric A ReitsPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 3, Iss 1, p e1503 (2008)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Hilde A Krol Przemek M Krawczyk Klazien S Bosch Jacob A Aten Elly M Hol Eric A Reits Polyglutamine expansion accelerates the dynamics of ataxin-1 and does not result in aggregate formation.
description	<h4>Background</h4>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.<h4>Methodology/principal findings</h4>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.<h4>Conclusions/significance</h4>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.
format	article
author	Hilde A Krol Przemek M Krawczyk Klazien S Bosch Jacob A Aten Elly M Hol Eric A Reits
author_facet	Hilde A Krol Przemek M Krawczyk Klazien S Bosch Jacob A Aten Elly M Hol Eric A Reits
author_sort	Hilde A Krol
title	Polyglutamine expansion accelerates the dynamics of ataxin-1 and does not result in aggregate formation.
title_short	Polyglutamine expansion accelerates the dynamics of ataxin-1 and does not result in aggregate formation.
title_full	Polyglutamine expansion accelerates the dynamics of ataxin-1 and does not result in aggregate formation.
title_fullStr	Polyglutamine expansion accelerates the dynamics of ataxin-1 and does not result in aggregate formation.
title_full_unstemmed	Polyglutamine expansion accelerates the dynamics of ataxin-1 and does not result in aggregate formation.
title_sort	polyglutamine expansion accelerates the dynamics of ataxin-1 and does not result in aggregate formation.
publisher	Public Library of Science (PLoS)
publishDate	2008
url	https://doaj.org/article/331efd107d164418ade7f1f56bb701eb
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Polyglutamine expansion accelerates the dynamics of ataxin-1 and does not result in aggregate formation.

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