与人类疾病相关的肌醇1,4,5-三磷酸受体突变
Inositol 1,4,5-trisphosphate Receptor Mutations associated with Human Disease.
作者信息
Terry Lara E, Alzayady Kamil J, Furati Esraa, Yule David I
机构信息
Department of Pharmacology and Physiology, University of Rochester, Rochester, New York 14642.
出版信息
Messenger (Los Angel). 2018 Jun;6(1-2):29-44.
Abstract
Calcium release into the cytosol via the inositol 1,4,5-trisphosphate receptor (IPR) calcium channel is important for a variety of cellular processes. As a result, impairment or inhibition of this release can result in disease. Recently, mutations in all four domains of the IPR have been suggested to cause diseases such as ataxia, cancer, and anhidrosis; however, most of these mutations have not been functionally characterized. In this review we summarize the reported mutations, as well as the associated symptoms. Additionally, we use clues from transgenic animals, receptor stoichiometry, and domain location of mutations to speculate on the effects of individual mutations on receptor structure and function and the overall mechanism of disease.
摘要
通过肌醇1,4,5-三磷酸受体（IPR）钙通道将钙释放到细胞质中对多种细胞过程都很重要。因此，这种释放的受损或抑制会导致疾病。最近，有人提出IPR所有四个结构域中的突变会导致共济失调、癌症和无汗症等疾病；然而，这些突变中的大多数尚未进行功能表征。在这篇综述中，我们总结了已报道的突变以及相关症状。此外，我们利用来自转基因动物、受体化学计量学和突变结构域位置的线索，推测单个突变对受体结构和功能的影响以及疾病的整体机制。
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