Expression of mutant huntingtin blocks exocytosis in PC12 cells by depletion of complexin II
Expression of mutant huntingtin blocks exocytosis in PC12 cells by depletion of complexin II
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DOI：
10.1074/jbc.m304615200
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发表时间：
2003-08-15
影响因子：
4.8
通讯作者：
Morton, AJ
中科院分区：
文献类型：
--
作者：
Edwardson, JM;Wang, CT;Morton, AJ
亨廷顿舞蹈病（HD）是一种常染色体显性神经退行性疾病，由亨廷顿舞蹈病基因CAG重复扩增引起。我们最近报道了复杂蛋白II，一种参与神经递质释放的蛋白质，在携带HD突变的小鼠的大脑和死后HD大脑的纹状体中都被耗尽。在这里，我们表明，在表达HD突变的PC12细胞中，复合体II的损失重现，并伴随着Ca2+触发的神经递质胞吐的急剧下降。过度表达络合素II（而不是络合素I）挽救了胞吐，这表明神经递质释放的下降是络合素II耗竭的直接后果。复合体II在脑部的耗竭可能是HD相关神经传递异常的原因。
Huntington's disease (HD) is an autosomal dominant neurodegenerative disorder caused by an expanded CAG repeat in the HD gene. We reported recently that complexin II, a protein involved in neurotransmitter release, is depleted from both the brains of mice carrying the HD mutation and from the striatum of post mortem HD brains. Here we show that this loss of complexin II is recapitulated in PC12 cells expressing the HD mutation and is accompanied by a dramatic decline in Ca2+-triggered exocytosis of neurotransmitter. Overexpression of complexin II (but not complexin I) rescued exocytosis, demonstrating that the decline in neurotransmitter release is a direct consequence of complexin II depletion. Complexin II depletion in the brain may account for some of the abnormalities in neurotransmission associated with HD.