Huntingtin-associated protein (HAP1): Discrete neuronal localizations in the brain resemble those of neuronal nitric oxide synthase
Huntingtin-associated protein (HAP1): Discrete neuronal localizations in the brain resemble those of neuronal nitric oxide synthase
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DOI：
10.1073/pnas.93.10.4839
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发表时间：
1996-05-14
影响因子：
11.1
通讯作者：
Ross, CA
中科院分区：
文献类型：
--
作者：
Li, XJ;Sharp, AH;Ross, CA
亨廷顿病源于亨廷顿蛋白的突变，其特征在于脑中离散神经元群体的选择性丧失。尽管纹状体中的神经元大量丢失，但产生NO的神经元完好无损。我们最近发现了一种与亨廷顿蛋白相关的脑特异性蛋白质，称为亨廷顿蛋白相关蛋白（HAP 1）。我们现在描述HAP 1的选择性神经元定位。原位杂交研究揭示了相似的HAP 1和神经元型一氧化氮合酶（nNOS）mRNA的本地化与戏剧性的富集都在脚桥核，副嗅球，视上核的下丘脑。nNOS和HAP 1都富含含有突触囊泡的亚细胞组分。免疫细胞化学研究表明HAP 1和nNOS在某些神经元中共存。HAP 1和nNOS在脑中的可能关系使人想起骨骼肌中肌营养不良蛋白和nNOS的关系，并表明NO在亨廷顿病中的作用，类似于其在杜氏肌营养不良症中的假定作用。
Huntington disease stems from a mutation of the protein huntingtin and is characterized by selective loss of discrete neuronal populations in the brain. Despite a massive loss of neurons in the corpus striatum, NO-generating neurons are intact. We recently identified a brain-specific protein that associates with huntingtin and is designated huntingtin-associated protein (HAP1). We now describe selective neuronal localizations of HAP1. In situ hybridization studies reveal a resemblance of HAP1 and neuronal nitric oxide synthase (nNOS) mRNA localizations with dramatic enrichment of both in the pedunculopontine nuclei, the accessory olfactory bulb, and the supraoptic nucleus of the hypothalamus. Both nNOS and HAP1 are enriched in subcellular fractions containing synaptic vesicles. Immunocytochemical studies indicate colocalizations of HAP1 and nNOS in some neurons. The possible relationship of HAP1 and nNOS in the brain is reminiscent of the relationship of dystrophin and nNOS in skeletal muscle and suggests a role of NO in Huntington disease, analogous to its postulated role in Duchenne muscular dystrophy.