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. 2003 May 8;38(3):375-87.
doi: 10.1016/s0896-6273(03)00258-7.

Serine 776 of ataxin-1 is critical for polyglutamine-induced disease in SCA1 transgenic mice

Effat S Emamian  1 , Michael D Kaytor, Lisa A Duvick, Tao Zu, Susan K Tousey, Huda Y Zoghbi, H Brent Clark, Harry T Orr
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Serine 776 of ataxin-1 is critical for polyglutamine-induced disease in SCA1 transgenic mice

Effat S Emamian et al. Neuron. .
Free article

Abstract

Polyglutamine-induced neurodegeneration in transgenic mice carrying the spinocerebellar ataxia type 1 (SCA1) gene is modulated by subcellular distribution of ataxin-1 and by components of the protein folding/degradation machinery. Since phosphorylation is a prominent mechanism by which these processes are regulated, we examined phosphorylation of ataxin-1 and found that serine 776 (S776) was phosphorylated. Residue 776 appeared to affect cellular deposition of ataxin-1[82Q] in that ataxin-1[82Q]-A776 failed to form nuclear inclusions in tissue culture cells. The importance of S776 for polyglutamine-induced pathogenesis was examined by generating ataxin-1[82Q]-A776 transgenic mice. These mice expressed ataxin-1[82Q]-A776 within Purkinje cell nuclei, yet the ability of ataxin-1[82Q]-A776 to induce disease was substantially reduced. These studies demonstrate that polyglutamine tract expansion and localization of ataxin-1 to the nucleus of Purkinje cells are not sufficient to induce disease. We suggest that S776 of ataxin-1 also has a critical role in SCA1 pathogenesis.

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