Journal Article

Ataxin-2 and huntingtin interact with endophilin-A complexes to function in plastin-associated pathways

Markus Ralser, Ute Nonhoff, Mario Albrecht, Thomas Lengauer, Erich E. Wanker, Hans Lehrach and Sylvia Krobitsch

in Human Molecular Genetics

Volume 14, issue 19, pages 2893-2909
Published in print October 2005 | ISSN: 0964-6906
Published online August 2005 | e-ISSN: 1460-2083 | DOI: http://dx.doi.org/10.1093/hmg/ddi321
Ataxin-2 and huntingtin interact with endophilin-A complexes to function in plastin-associated pathways

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Spinocerebellar ataxia type 2 is an inherited neurodegenerative disorder that is caused by an expanded trinucleotide repeat in the SCA2 gene, encoding a polyglutamine stretch in the gene product ataxin-2. Although evidence has been provided that ataxin-2 is involved in RNA metabolism, the physiological function of ataxin-2 remains unclear. Here, we demonstrate that ataxin-2 interacts with two members of the endophilin family, endophilin-A1 and endophilin-A3. To elucidate the physiological implications of these interactions, we exploited yeast as a model system and discovered that expression of ataxin-2 as well as both endophilin proteins is toxic for yeast lacking the SAC6 gene product fimbrin, a protein involved in actin filament organization and endocytotic processes. Intriguingly, expression of huntingtin, another polyglutamine protein interacting with endophilin-A3, was also toxic in Δsac6 yeast. These effects can be suppressed by simultaneous expression of one of the two human fimbrin orthologs, L- or T-plastin. Moreover, we have discovered that ataxin-2 associates with L- and T-plastin and that overexpression of ataxin-2 leads to accumulation of T-plastin in mammalian cells. Thus, our findings suggest an interplay between ataxin-2, endophilin proteins and huntingtin in plastin-associated cellular pathways.

Journal Article.  11822 words.  Illustrated.

Subjects: Genetics and Genomics

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