The cerebellar leucine-rich acidic nuclear protein interacts with ataxin-1
The cerebellar leucine-rich acidic nuclear protein interacts with ataxin-1
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DOI：
10.1038/40159
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发表时间：
1997-10-30
期刊：
影响因子：
64.8
通讯作者：
Zoghbi, HY
中科院分区：
文献类型：
--
作者：
Matilla, A;Koshy, BT;Zoghbi, HY
脊髓小脑性共济失调1型（SCA 1）是一种常染色体显性遗传神经退行性疾病，其特征为共济失调、进行性运动退化和小脑浦肯野细胞丢失（1）。SCA 1属于由CAG重复序列扩增引起的一组不断增长的神经退行性疾病，CAG重复序列编码谷氨酰胺（2）。尽管含有这些重复序列的蛋白质广泛表达，但SCA 1和其他多聚谷氨酰胺疾病中的神经变性选择性地涉及少数神经元亚型。这种神经元特异性的机制尚不清楚。在这里，我们发现小脑富含亮氨酸的酸性核蛋白（LANP）（3）与SCA 1基因产物共济失调蛋白-1相互作用。LANP主要在浦肯野细胞中表达，浦肯野细胞是SCAT的主要病理部位。当谷氨酰胺的数量增加时，LANP和共济失调蛋白-1之间的相互作用显著增强。免疫荧光研究表明，LANP和共济失调蛋白-1共定位于核基质相关的亚核结构。共济失调蛋白-1和LANP之间的相互作用的特点，其表达的空间和时间模式，以及共定位的研究表明，小脑LANP参与SCA 1的发病机制。
Spinocerebellar ataxia type 1 (SCA1) is an autosomal dominant neurodegenerative disorder characterized by ataxia, progressive motor deterioration, and loss of cerebellar Purkinje cells(1). SCA1 belongs to a growing group of neurodegenerative disorders caused by expansion of CAG repeats, which encode glutamine(2). Although the proteins containing these repeats are widely expressed, the neurodegeneration in SCA1 and other polyglutamine diseases selectively involves a few neuronal subtypes. The mechanism(s) underlying this neuronal specificity is unknown. Here we show that the cerebellar leucine-rich acidic nuclear protein (LANP)(3) interacts with ataxin-1, the SCA1 gene product. LANP is expressed predominantly in Purkinje cells, the primary site of pathology in SCAT. The interaction between LANP and ataxin-1 is significantly stronger when the number of glutamines is increased. Immunofluorescence studies demonstrate that both LANP and ataxin-1 colocalize in nuclear matrix-associated subnuclear structures. The features of the interaction between ataxin-1 and LANP, their spatial and temporal patterns of expression, and the colocalization studies indicate that cerebellar LANP is involved in the pathogenesis of SCA1.