Aberrant palmitoylation in Huntington disease.
Aberrant palmitoylation in Huntington disease.
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亨廷顿病中的异常棕榈酰化。
DOI：
10.1042/bst20140242
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发表时间：
2015
影响因子：
3.9
通讯作者：
M. Hayden
中科院分区：
文献类型：
--
作者：
Shaun S. Sanders;M. Hayden
亨廷顿病（HD）是由HTT基因中CAG扩增引起的成人发病的神经退行性疾病。HD的特征是纹状体萎缩，并与运动、认知和精神缺陷相关。在HD突变的存在下，亨廷顿蛋白（HTT）与亨廷顿蛋白相互作用蛋白14（HIP 14或DHHC 17）和HIP 14样（DHHC 13，HIP 14直向同源物）、HTT的棕榈酰酰基转移酶之间的相互作用受到干扰，导致HTT的棕榈酰化减少。Hip 14或Hip 14 l的基因消融概括了HD的许多特征，包括纹状体萎缩和运动缺陷。然而，在任一小鼠模型中HTT的棕榈酰化没有变化，随后，这两种小鼠模型和HD小鼠模型的表型之间的相似性被认为是由其他HIP 14和HIP 14 L底物的棕榈酰化不足引起的。HTT作为HIP 14活性的调节剂，使得在HD突变存在下，HIP 14活性较低。因此，HIP 14底物棕榈酰化较少，导致神经元毒性。这表明在HD突变存在下改变的HIP 14-HTT和HIP 14 L-HTT相互作用减少棕榈酰化并促进HTT和其他HIP 14/HIP 14 L底物的错误定位。最终，HD可能部分是棕榈酰化改变的疾病。
Huntington disease (HD) is an adult-onset neurodegenerative disease caused by a CAG expansion in the HTT gene. HD is characterized by striatal atrophy and is associated with motor, cognitive and psychiatric deficits. In the presence of the HD mutation, the interactions between huntingtin (HTT) and huntingtin interacting protein 14 (HIP14 or DHHC17) and HIP14-like (DHHC13, a HIP14 orthologue), palmitoyl acyltransferases for HTT, are disturbed, resulting in reduced palmitoylation of HTT. Genetic ablation of either Hip14 or Hip14l recapitulates many features of HD, including striatal atrophy and motor deficits. However, there are no changes in palmitoylation of HTT in either mouse model and, subsequently, the similarities between the phenotypes of these two mouse models and the HD mouse model are believed to result from underpalmitoylation of other HIP14 and HIP14L substrates. HTT acts as a modulator of HIP14 activity such that in the presence of the HD mutation, HIP14 is less active. Consequently, HIP14 substrates are less palmitoylated, leading to neuronal toxicity. This suggests that altered HIP14-HTT and HIP14L-HTT interactions in the presence of the HD mutation reduces palmitoylation and promotes mislocalization of HTT and other HIP14/HIP14L substrates. Ultimately, HD may be, in part, a disease of altered palmitoylation.
影响因子：
3.5
作者：
Singaraja, RR;Hadano, S;Hayden, MR
通讯作者：
Hayden, MR