Oligomerization of expanded-polyglutamine domain fluorescent fusion proteins in cultured mammalian cells.
Oligomerization of expanded-polyglutamine domain fluorescent fusion proteins in cultured mammalian cells.
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培养的哺乳动物细胞中扩展的聚谷氨酰胺结构域荧光融合蛋白的寡聚化。
DOI：
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发表时间：
1997
期刊：
影响因子：
--
通讯作者：
Warren J. Strittmatter
中科院分区：
文献类型：
--
作者：
Osamu Onodera;James R. Burke;Sara E. Miller;Susan Hester;Shoji Tsuji;A. D. Roses;Warren J. Strittmatter
包括亨廷顿病在内的六种遗传性神经疾病是由于疾病基因的CAG结构域扩大，在表达的蛋白质中产生了一个超过40个谷氨酸的结构域。这种聚谷氨酰胺结构域的扩展导致疾病的机制尚不清楚。最近的研究表明，哺乳动物神经元中存在多聚谷氨酰胺结构域蛋白的寡聚现象。为了研究聚谷氨酰胺蛋白的齐聚作用并鉴定异源蛋白的相互作用，在培养的COS-7细胞中表达了不同长度的聚谷氨酰胺-绿色荧光蛋白融合蛋白。19-和35-谷氨酰胺融合蛋白(非病理性长度)弥漫分布于细胞质。相比之下，56-和80-谷氨酰胺融合蛋白(病理长度)形成的纤维阵列与先前在亨廷顿病神经元和转基因小鼠模型中观察到的相似。这些集合体位于胞核内和胞浆内。胞质内聚集体被塌陷的中间丝包围。中间丝蛋白波形蛋白与扩展的聚谷氨酰胺融合蛋白免疫共分离。这一细胞模型将加速研究聚谷氨酰胺蛋白的寡聚化及其与其他蛋白的相互作用。
Six inherited neurologic diseases, including Huntington's disease, result from the expansion of a CAG domain of the disease genes to produce a domain of more than 40 glutamines in the expressed protein. The mechanism by which expansion of this polyglutamine domain causes disease is unknown. Recent studies demonstrated oligomerization of polyglutamine-domain proteins in mammalian neurons. To study oligomerization of polyglutamine proteins and to identify heterologous protein interactions, varying length polyglutamine-green fluorescent protein fusion proteins were expressed in cultured COS-7 cells. The 19- and 35-glutamine fusion proteins (non-pathologic length) distributed diffusely throughout the cytoplasm. In contrast, 56- and 80-glutamine fusion proteins (pathologic length) formed fibrillar arrays resembling those previously observed in neurons in Huntington's disease and in a transgenic mouse model. These aggregates were intranuclear and intracytoplasmic. Intracytoplasmic aggregates were surrounded by collapsed intermediate filaments. The intermediate filament protein vimentin co-immunoisolated with expanded polyglutamine fusion proteins. This cellular model will expedite investigations into oligomerization of polyglutamine proteins and their interactions with other proteins.
影响因子：
4
作者：
Trevor,KT;McGuire,JG;Leonova,EV
通讯作者：
Leonova,EV
DOI：
10.1073/pnas.92.19.8710
发表时间：
1995-09-12
影响因子：
11.1
作者：
GUTEKUNST, CA;LEVEY, AI;HERSCH, SM
通讯作者：
HERSCH, SM
谷氨酰胺重复序列的掺入使蛋白质寡聚化：对神经退行性疾病的影响。
DOI：
10.1073/pnas.92.14.6509
发表时间：
1995
影响因子：
11.1
作者：
Stott,K;Blackburn,JM;Butler,PJ;Perutz,M
通讯作者：
Perutz,M