Junctophilin 2功能异常与心脏疾病的研究进展

Research progress in Junctophilin 2 dysfunction and heart disease

耦联膜复合物(Junctional membrane complexes,JMCs)是20世纪50年代中期首先在肌细胞中发现的[1]。JMCs存在于所有可兴奋细胞质膜(plasma membrane,PM)和内质网/肌浆网(endoplasmic/sarcoplasmic reticulum,ER/SR)之间,是实现PM与ER/SR间信号交互的一种特殊亚细胞结构域。Junctophilin(JP, JPH)蛋白是2000年[2]由日本东京大学Takeshima研究小组发现并鉴定的,JPH蛋白是参与耦联膜复合物(JMCs)形成和维持的关键性结构蛋白家族。目前已发现该蛋白家族包括JPH1、JPH2、JPH3和JPH4四种亚型,它们分别分布于不同组织中,JPH1和JPH2主要存在于骨骼肌细胞、心肌细胞及平滑肌细胞,而JPH3和JPH4主要存在于中枢神经系统。Junctophilin 2(JPH2)在心脏中广泛表达,是心肌细胞内参与耦联膜复合物JMCs形成和维持的关键结构蛋白。当JPH2出现基因突变、表达下调以及内部空间分布紊乱等功能异常时,可导致一系列的心脏疾病。

Junctional membrane complexes （JMCs） were first discovered in muscle cells in the mid-1950s[1].JMCs, as a special subcellular domain for signal communication between plasma membrane （PM） and endoplasmic/sarcoplasmic reticulum （ER/SR）, are located between the PM and ER/SR in all excitable cells. Junctophilin （JP,JPH） protein, discovered and identified by Takeshima research group from the University of Tokyo in 2000[2], is a keystructural protein family involved in the formation and maintenance of JMCs. The protein family includes four sub-types, i.e., JPH1, JPH2, JPH3, and JPH4, which are distributed in different tissues. JPH1 and JPH2 are mainlyfound in skeletal muscle cells, cardiomyocytes, and smooth muscle cells, while JPH3 and JPH4 are mainly found inthe central nervous system. JPH2 is widely expressed in cardiac myocytes and is a key structural protein involved inthe formation and maintenance of the JMCs in cardiac myocytes. A series of heart diseases can be initiated whengene mutation, down-regulation of gene expression, or disturbed spatial distribution occurs in JPH2.