Lagalwar Sarita, Orr Harry T
Institute for Translational Neuroscience, University of Minnesota, Minneapolis, MN, USA.
Methods Mol Biol. 2013;1010:201-9. doi: 10.1007/978-1-62703-411-1_13.
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.
共济失调蛋白-1（Ataxin-1）的蛋白表达存在于浦肯野细胞的细胞质和细胞核中，浦肯野细胞是1型脊髓小脑共济失调（SCA1）的主要发病部位。S776位点的磷酸化发生在细胞质中，并通过与14-3-3相互作用使蛋白稳定，从而使其能够转运到引发疾病的细胞核中。当存在多聚谷氨酰胺扩增时，磷酸化和稳定性会增强。在本章中，我们提出了一个SCA1神经退行性变的模型：由环磷酸腺苷（cAMP）依赖性蛋白激酶（PKA）在S776位点磷酸化引发，并因多聚谷氨酰胺扩增的存在而增强。文中描述了用于揭示SCA1发病机制和S776位点磷酸化的生物学方法。
