α Pix enhances mutant huntingtin aggregation
α Pix enhances mutant huntingtin aggregation
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DOI：
10.1016/j.jns.2009.11.003
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发表时间：
2010-03-15
影响因子：
4.4
通讯作者：
Rubinsztein, David C.
中科院分区：
文献类型：
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作者：
Eriguchi, Makoto;Mizuta, Haruo;Rubinsztein, David C.
亨廷顿氏病是由聚谷氨酰胺扩展突变亨廷顿蛋白（muhtt）引起的，这是一种易于聚集的蛋白。在筛选肌动蛋白-细胞骨架组织相关因子后，我们确定了pak相互作用交换因子（alpha Pix/Cool2）是一种新的亨廷顿蛋白（htt）相互作用蛋白。通过免疫沉淀实验，我们发现alpha Pix可以结合野生型htt （wthtt）和突变型htt （muthtt）的n端。共定位研究表明（x Pix）在真菌聚集体中积累。缺失分析表明，Pix与htt相互作用需要dbl同源结构域（DH）和pleckstrin同源结构域（PH）。Pix的过表达通过诱导sds可溶菌体-菌体相互作用增强菌体聚集。相反，敲低Pix会减弱mutt聚集。这些发现表明Pix在真菌聚集中起重要作用。(C) 2009 Elsevier B.V.版权所有
Huntington's disease is caused by polyglutamine-expanded mutant huntingtin (muhtt), an aggregation-prone protein. We identified the Pak-interacting exchange factor (alpha Pix/Cool2) as a novel huntingtin (htt) interacting protein, after screening actin-cytoskeleton organization-related factors. Using immunoprecipitation experiments, we show that alpha Pix binds to both the N-terminal of wild-type htt (wthtt) and mutant htt (muthtt). Colocalization studies revealed that (x Pix accumulates in muthtt aggregates. Deletion analysis suggested that the dbl homology (DH) and pleckstrin homology (PH) domains of alpha Pix are required for its interaction with htt. Overexpression of ot Pix enhanced muthtt aggregation by inducing SDS-soluble muthtt-muthtt interactions. Conversely, knocking down ot Pix attenuated muhtt aggregation. These findings suggest that ot Pix plays an important role in muthtt aggregation. (C) 2009 Elsevier B.V. All rights reserved.