The actinin family of actin cross-linking proteins - a genetic perspective.
The actinin family of actin cross-linking proteins - a genetic perspective.
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DOI：
10.1186/s13578-015-0029-7
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发表时间：
2015
影响因子：
7.5
通讯作者：
Young PW
中科院分区：
文献类型：
--
作者：
Murphy AC;Young PW
肌动蛋白是在几乎所有细胞类型中发现的主要肌动蛋白交联蛋白之一，是一个更大家族的祖先蛋白，包括spectrin， dystrophin和utrophin。无脊椎动物只有一个编码肌动蛋白的ACTN基因，而哺乳动物有四个。人类所有四种基因的突变现在都与遗传性疾病或性状有关。ACTN1突变导致大量血小板减少症，这是一种以大量出血为特征的血小板疾病。ACTN2突变与一系列心肌病有关，ACTN4突变引起一种称为局灶节段性肾小球硬化的肾脏疾病。有趣的是，全世界约有16%的人是ACTN3无义突变的纯合子，这种突变会消除actin -3蛋白的表达。这个ACTN3空等位基因最近在特定人群中经历了正选择，这可能与提高耐力和适应寒冷气候有关。在这篇综述中，我们讨论了ACTN基因家族的人类遗传学，以及几种模式生物中ACTN基因敲除的研究。来自这两个领域的观察提供了对肌动蛋白的进化和细胞功能的见解。本文的在线版本（doi:10.1186/s13578-015-0029-7）包含补充材料，仅供授权用户使用。
Actinins are one of the major actin cross-linking proteins found in virtually all cell types and are the ancestral proteins of a larger family that includes spectrin, dystrophin and utrophin. Invertebrates have a single actinin-encoding ACTN gene, while mammals have four. Mutations in all four human genes have now been linked to heritable diseases or traits. ACTN1 mutations cause macrothrombocytopenia, a platelet disorder characterized by excessive bleeding. ACTN2 mutations have been linked to a range of cardiomyopathies, and ACTN4 mutations cause a kidney condition called focal segmental glomerulosclerosis. Intriguingly, approximately 16 % of people worldwide are homozygous for a nonsense mutation in ACTN3 that abolishes actinin-3 protein expression. This ACTN3 null allele has undergone recent positive selection in specific human populations, which may be linked to improved endurance and adaptation to colder climates. In this review we discuss the human genetics of the ACTN gene family, as well as ACTN gene knockout studies in several model organisms. Observations from both of these areas provide insights into the evolution and cellular functions of actinins. The online version of this article (doi:10.1186/s13578-015-0029-7) contains supplementary material, which is available to authorized users.