Institute of Molecular Medicine, Peking University, Beijing 100871, China.
J Mol Cell Biol. 2010 Apr;2(2):96-102. doi: 10.1093/jmcb/mjp038. Epub 2009 Dec 30.
Actinin-associated LIM protein (ALP) and Enigma are two subfamilies of Postsynaptic density 95, discs large and zonula occludens-1 (PDZ)-Lin-11, Isl1 and Mec-3 (LIM) domain containing proteins. ALP family members have one PDZ and one LIM domain, whereas Enigma proteins contain one PDZ and three LIM domains. Four ALP and three Enigma proteins have been identified in mammals, each having multiple splice variants and unique expression patterns. Functionally, these proteins bind through their PDZ domains to alpha-actinin and bind through their LIM domains or other internal protein interaction domains to other proteins, including signaling molecules. ALP and Enigma proteins have been implicated in cardiac and skeletal muscle structure, function and disease, neuronal function, bipolar disorder, tumor growth, platelet and epithelial cell motility and bone formation. This review will focus on recent advances in the biological roles of ALP/Enigma PDZ-LIM domain proteins in cardiac muscle and provide insights into mechanisms by which mutations in these proteins are related to human cardiac disease.
肌动蛋白结合 LIM 蛋白 (ALP) 和 Enigma 是 Postsynaptic density 95、Discs large 和 zonula occludens-1 (PDZ)-Lin-11、Isl1 和 Mec-3 (LIM) 结构域蛋白的两个亚家族。ALP 家族成员具有一个 PDZ 和一个 LIM 结构域，而 Enigma 蛋白含有一个 PDZ 和三个 LIM 结构域。哺乳动物中已鉴定出四种 ALP 和三种 Enigma 蛋白，每种蛋白都有多个剪接变体和独特的表达模式。在功能上，这些蛋白通过其 PDZ 结构域与肌动蛋白结合，并通过其 LIM 结构域或其他内部蛋白相互作用结构域与其他蛋白结合，包括信号分子。ALP 和 Enigma 蛋白已被证明与心脏和骨骼肌的结构、功能和疾病、神经元功能、双相情感障碍、肿瘤生长、血小板和上皮细胞迁移以及骨形成有关。这篇综述将重点介绍 ALP/Enigma PDZ-LIM 结构域蛋白在心肌中的生物学作用的最新进展，并深入了解这些蛋白中的突变与人类心脏疾病的关系的机制。
