Expanded polyglutamines impair synaptic transmission and ubiquitin-proteasome system in Caenorhabditis elegans
Expanded polyglutamines impair synaptic transmission and ubiquitin-proteasome system in Caenorhabditis elegans
复制标题
DOI：
10.1111/j.1471-4159.2006.03895.x
复制
发表时间：
2006-07-01
影响因子：
4.7
通讯作者：
Nukina, Nobuyuki
中科院分区：
文献类型：
--
作者：
Khan, Liakot A.;Bauer, Peter O.;Nukina, Nobuyuki
多聚谷氨酰胺（polyQ）在许多蛋白质中的扩增，包括亨廷顿蛋白和共济失调蛋白-3，是致病性的，并导致神经元功能障碍和变性。虽然至少有九种神经退行性疾病是由扩展的polyQ引起的，但这些疾病的发病机制仍不清楚。在本研究中，我们使用秀丽隐杆线虫来研究polyQ介导的毒性的分子机制。我们在C.优雅我们发现，扩大polyQ中断突触传递，并诱导肿胀和异常分支的神经元过程。利用泛素化的荧光报告构建体，我们还发现polyQ聚集体损害了C.优雅这些结果可能为进一步了解polyQ疾病的发病机制提供信息。
Polyglutamine (polyQ) expansion in many proteins, including huntingtin and ataxin-3, is pathogenic and responsible for neuronal dysfunction and degeneration. Although at least nine neurodegenerative diseases are caused by expanded polyQ, the pathogenesis of these diseases is still not well understood. In the present study, we used Caenorhabditis elegans to study the molecular mechanism of polyQ-mediated toxicity. We expressed full-length and truncated ataxin-3 with different lengths of polyQ in the nervous system of C. elegans. We show that expanded polyQ interrupts synaptic transmission, and induces swelling and aberrant branching of neuronal processes. Using an ubiquitinated fluorescence reporter construct, we also showed that polyQ aggregates impair the ubiquitin-proteasome system in C. elegans. These results may provide information for further understanding the pathogenesis of polyQ diseases.