Transglutaminase 6 interacts with polyQ proteins and promotes the formation of polyQ aggregates
Transglutaminase 6 interacts with polyQ proteins and promotes the formation of polyQ aggregates
复制标题
转谷氨酰胺酶 6 与 PolyQ 蛋白相互作用并促进 PolyQ 聚集体的形成
DOI：
10.1016/j.bbrc.2013.06.044
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发表时间：
2013-07-19
影响因子：
3.1
通讯作者：
Wang, Jun-Ling
中科院分区：
文献类型：
--
作者：
Guan, Wen-Juan;Xia, Kai-De;Wang, Jun-Ling
多聚谷氨酰胺（polyQ）疾病的一个共同特征是由扩展的多聚谷氨酰胺束引起的神经元细胞中的聚集体的存在。PolyQ蛋白是转氨酶2的底物，并且在PolyQ疾病中转氨酶的活性增加表明转氨酶可能直接参与聚集体的形成。我们以前确定转氨酶6基因是脊髓小脑共济失调35型（SCA35）的病因，我们发现SCA35相关的突变体表现出降低转氨酶活性。在这里，我们报告，转氨酶6相互作用，并与HEK293细胞中的正常和扩展的polyQ蛋白共定位。此外，转氨酶6的过表达促进polyQ聚集体的形成和可溶性polyQ向不溶性polyQ聚集体的转化。然而，SCA35相关突变体不影响它们与polyQ蛋白的相互作用。这些数据表明，转氨酶6可能参与polyQ疾病，polyQ相关SCA和SCA之间可能存在共同的病理联系35。(c)2013 Elsevier Inc. All rights reserved.
A common feature of polyglutamine (polyQ) diseases is the presence of aggregates in neuronal cells caused by expanded polyglutamine tracts. PolyQ proteins are the substrates of transglutaminase 2, and the increased activity of transglutaminase in polyQ diseases suggests that transglutaminase may be directly involved in the formation of the aggregates. We previously identified the transglutaminase 6 gene to be causative of spinocerebellar ataxia type 35 (SCA35), and we found that SCA35-associated mutants exhibited reduced transglutaminase activity. Here we report that transglutaminase 6 interacts and co-localizes with both normal and expanded polyQ proteins in HEK293 cells. Moreover, the overexpression of transglutaminase 6 promotes the formation of polyQ aggregates and the conversion of soluble polyQ into insoluble polyQ aggregates. However, SCA35-associated mutants do not affect their interactions with polyQ proteins. These data suggest that transglutaminase 6 could be involved in polyQ diseases and there may exist a common pathological link between polyQ associated SCA and SCA35. (c) 2013 Elsevier Inc. All rights reserved.