Department of Biology, University of Iowa, Iowa City, IA 52242, USA.
Front Biosci (Landmark Ed). 2012 Jun 1;17(7):2566-93. doi: 10.2741/4072.
Intercalated discs (ICDs) are cardiac-specific structures responsible for mechanical and electrical communication among adjacent cardiomyocytes and are implicated in signal transduction. The striated muscle-specific Xin repeat-containing proteins localize to ICDs and play critical roles in ICD formation and cardiac function. Knocking down the Xin gene in chicken embryos collapses the wall of developing heart chambers and leads to abnormal cardiac morphogenesis. In mammals, a pair of paralogous genes, Xinalpha and Xinbeta exist. Ablation of the mouse Xinalpha (mXinalpha) does not affect heart development. Instead, mXinalpha-deficient mice show adult late-onset cardiac hypertrophy and cardiomyopathy with conduction defects. The mXinalpha-deficient hearts up-regulate mouse Xinbeta (mXinbeta, suggesting a partial compensatory role of mXinbeta. Complete loss of mXinbeta however, leads to failure of forming ICD, mis-localization of mXinalpha, and early postnatal lethality. In this review, we will briefly discuss recent advances in the anatomy and function of ICDs. We will then review what we know about Xin repeat-containing proteins and how this protein family promotes ICD maturation and stability for normal cardiac function.
闰盘是心脏特有的结构，负责连接相邻心肌细胞的机械和电通讯，并参与信号转导。横纹肌特异性的 Xin 重复蛋白定位于闰盘，对于闰盘的形成和心脏功能具有关键作用。敲除鸡胚胎中的 Xin 基因，会导致正在发育的心脏腔室壁崩溃，并导致心脏畸形。在哺乳动物中，存在一对 Xinalpha 和 Xinbeta 这两个平行基因。敲除小鼠的 Xinalpha(mXinalpha) 不会影响心脏发育。相反，mXinalpha 缺失的小鼠表现为成年后期出现心脏肥大和心肌病，并伴有传导缺陷。mXinalpha 缺失的心脏上调表达小鼠的 Xinbeta(mXinbeta)，表明 mXinbeta 具有部分补偿作用。然而，当完全缺失 mXinbeta 时，会导致闰盘形成失败、mXinalpha 定位错误，以及出生后早期死亡。在这篇综述中，我们将简要讨论闰盘的解剖结构和功能的最新进展。然后，我们将回顾一下关于 Xin 重复蛋白的知识，以及这个蛋白家族如何促进闰盘成熟和稳定性，从而维持正常的心脏功能。
