Otto Warburg Laboratory, Max Planck Institute for Molecular Genetics, Berlin, Germany.
PLoS One. 2012;7(11):e50134. doi: 10.1371/journal.pone.0050134. Epub 2012 Nov 27.
Paralogs for several proteins implicated in neurodegenerative disorders have been identified and explored to further facilitate the identification of molecular mechanisms contributing to disease pathogenesis. For the disease-causing protein in spinocerebellar ataxia type 2, ataxin-2, a paralog of unknown function, termed ataxin-2-like, has been described. We discovered that ataxin-2-like associates with known interaction partners of ataxin-2, the RNA helicase DDX6 and the poly(A)-binding protein, and with ataxin-2 itself. Furthermore, we found that ataxin-2-like is a component of stress granules. Interestingly, sole ataxin-2-like overexpression led to the induction of stress granules, while a reduction of stress granules was detected in case of a low ataxin-2-like level. Finally, we observed that overexpression of ataxin-2-like as well as its reduction has an impact on the presence of microscopically visible processing bodies. Thus, our results imply a functional overlap between ataxin-2-like and ataxin-2, and further indicate a role for ataxin-2-like in the regulation of stress granules and processing bodies.
已经鉴定出几种与神经退行性疾病相关的蛋白质的旁系同源物，并对其进行了探索，以进一步促进鉴定导致疾病发病机制的分子机制。对于脊髓小脑共济失调 2 型的致病蛋白，ataxin-2，一种未知功能的旁系同源物，称为ataxin-2-like，已经被描述。我们发现 ataxin-2-like 与已知的 ataxin-2 相互作用伙伴，RNA 解旋酶 DDX6 和多聚（A）结合蛋白，以及 ataxin-2 本身相互作用。此外，我们发现 ataxin-2-like 是应激颗粒的组成部分。有趣的是，仅 ataxin-2-like 的过表达导致应激颗粒的诱导，而在 ataxin-2-like 水平较低的情况下检测到应激颗粒的减少。最后，我们观察到 ataxin-2-like 的过表达以及其减少对显微镜可见的处理体的存在有影响。因此，我们的结果表明 ataxin-2-like 和 ataxin-2 之间存在功能重叠，并进一步表明 ataxin-2-like 在应激颗粒和处理体的调节中起作用。
