Ataxin-1 protein expression is found in the cytoplasm and nucleus of Purkinje cells, the primary site of spinocerebellar ataxia type 1 (SCA1). Phosphorylation at S776 occurs in the cytoplasm and stabilizes the protein through interaction with 14-3-3, allowing it to translocate into the nucleus where disease is initiated. Phosphorylation and stabilization are enhanced when the polyglutamine expansion is present. In this chapter, we present a model of neurodegeneration in SCA1 initiated through phosphorylation at S776 by cAMP-dependent protein kinase (PKA) and enhanced by the presence of the polyglutamine expansion. The biological methods used to uncover SCA1 pathogenesis and phosphorylation at S776 are described. © Springer Science+Business Media New York 2013.
CITATION STYLE
Lagalwar, S., & Orr, H. T. (2013). Regulation of ataxin-1 phosphorylation and its impact on biology. Methods in Molecular Biology, 1010, 201–209. https://doi.org/10.1007/978-1-62703-411-1_13
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