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

Item Type:	Article
Title:	Ataxin-2 and huntingtin interact with endophilin-A complexes to function in plastin-associated pathways
Creators Name:	Ralser, M. and Nonhoff, U. and Albrecht, M. and Lengauer, T. and Wanker, E.E. and Lehrach, H. and Krobitsch, S.
Abstract:	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.
Keywords:	Amino Acid Sequence, Adaptor Proteins, Cultured Cells, Cytoplasm, Gene Deletion, Intracellular Signaling Peptides and Proteins, Membrane Glycoproteins, Microfilament Proteins, Molecular Sequence Data, Nerve Tissue Proteins, Nuclear Proteins, Phosphoproteins, Saccharomyces cerevisiae, Signal Transducing , Spinocerebellar Ataxias, Src Homology Domains, Transcriptional Activation, Two-Hybrid System Techniques, Animals, Mice
Source:	Human Molecular Genetics
ISSN:	0964-6906
Publisher:	Oxford University Press
Volume:	14
Number:	19
Page Range:	2893-2909
Date:	22 August 2005
Official Publication:	https://doi.org/10.1093/hmg/ddi321
PubMed:	View item in PubMed

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