HUNTINGTIN IS A CYTOPLASMIC PROTEIN ASSOCIATED WITH VESICLES IN HUMAN AND RAT-BRAIN NEURONS
HUNTINGTIN IS A CYTOPLASMIC PROTEIN ASSOCIATED WITH VESICLES IN HUMAN AND RAT-BRAIN NEURONS
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DOI：
10.1016/0896-6273(95)90346-1
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发表时间：
1995-05-01
期刊：
影响因子：
16.2
通讯作者：
ARONIN, N
中科院分区：
文献类型：
--
作者：
DIFIGLIA, M;SAPP, E;ARONIN, N
亨廷顿病中的缺陷基因编码一种功能未知的蛋白质--亨廷顿蛋白。针对亨廷顿蛋白三个不同区域产生的抗血清在人神经母细胞瘤提取物的免疫印迹上鉴定出一种与320 kDa相似的高分子量蛋白质。在人和大鼠皮质突触体和富含囊泡的部分的蔗糖密度梯度中也检测到相同的蛋白质种类，其中Huntingtin免疫反应与囊泡膜蛋白(SV2、转铁蛋白受体和突触素)的分布重叠。人和大鼠脑内的免疫组织化学显示，亨廷顿蛋白广泛存在于神经元，特别是胞体和树突中，而不是许多囊泡相关蛋白所特有的更具选择性的轴突末端标记模式。在超微结构水平上，皮质神经元的免疫反应位于细胞质基质和囊泡周围的膜上。亨廷顿蛋白在神经元中的广泛胞浆分布及其与小泡的联系表明，亨廷顿蛋白可能在小泡运输中起作用。
The gene defective in Huntington's disease encodes a protein, huntingtin, with unknown function. Antisera generated against three separate regions of huntingtin identified a single high molecular weight protein of similar to 320 kDa on immunoblots of human neuroblastoma extracts. The same protein species was detected in human and rat cortex synaptosomes and in sucrose density gradients of vesicle-enriched fractions, where huntingtin immunoreactivity overlapped with the distribution of vesicle membrane proteins (SV2, transferrin receptor, and synaptophysin). Immunohistochemistry in human and rat brain revealed widespread cytoplasmic labeling of huntingtin within neurons, particularly cell bodies and dendrites, rather than the more selective pattern of axon terminal labeling characteristic of many vesicle-associated proteins. At the ultrastructural level, immunoreactivity in cortical neurons was detected in the matrix of the cytoplasm and around the membranes of the vesicles. The ubiquitous cytoplasmic distribution of huntingtin in neurons and its association with vesicles suggest that huntingtin may have a role in vesicle trafficking.