GJA1-20k and Mitochondrial Dynamics.
GJA1-20k and Mitochondrial Dynamics.
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DOI：
10.3389/fphys.2022.867358
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发表时间：
2022
影响因子：
4
通讯作者：
Shaw RM
中科院分区：
文献类型：
--
作者：
Shimura D;Shaw RM
连接蛋白43 （Connexin 43, Cx43）是哺乳动物心脏心室的主要间隙连接蛋白，由基因Gja1编码，Gja1具有单个编码外显子，因此不能剪切。我们之前发现，Gja1 mRNA在几个内部AUG (M)起始密码子之一处进行内源性内部翻译，产生n端截断的蛋白同工型，将c端保留在起始位点的远端。GJA1-20k的翻译始于mRNA M213，通常是细胞中最丰富的异构体，在缺血和代谢应激后显著增加。GJA1-20k由Cx43最后跨膜结构域的一小段和完整的c端尾部组成，总大小约为20 kDa。GJA1-20k最初的作用是作为一个重要的亚基，促进全长Cx43六聚体半通道的运输到细胞-细胞接触，在心肌中产生相邻细胞之间的传统间隙连接，促进电兴奋的有效传播。Gja1 -20k缺陷小鼠（由Gja1的M213L取代产生）在出生后2至4周心肌细胞之间的电偶联不良和心律失常性猝死。我们最近发现外源性GJA1-20k表达也模仿小鼠心脏缺血预处理的作用。此外，GJA1-20k定位于线粒体外膜，诱导线粒体分裂的保护性和DRP1独立形式，在代谢应激下保持ATP的产生和产生较少的活性氧（ROS），为心肌缺血损伤提供强大的保护。在这篇文章中，我们重点关注GJA1-20k在线粒体中的详细作用，以及它与肌动蛋白细胞骨架的相互作用。
Connexin 43 (Cx43) is the primary gap junction protein of mammalian heart ventricles and is encoded by the gene Gja1 which has a single coding exon and therefore cannot be spliced. We previously identified that Gja1 mRNA undergoes endogenous internal translation initiated at one of several internal AUG (M) start codons, generating N-terminal truncated protein isoforms that retain the C-terminus distal to the start site. GJA1-20k, whose translation initiates at mRNA M213, is usually the most abundant isoform in cells and greatly increases after ischemic and metabolic stress. GJA1-20k consists of a small segment of the last transmembrane domain and the complete C-terminus tail of Cx43, with a total size of about 20 kDa. The original role identified for GJA1-20k is as an essential subunit that facilitates the trafficking of full-length Cx43 hexameric hemichannels to cell-cell contacts, generating traditional gap junctions between adjacent cells facilitating, in cardiac muscle, efficient spread of electrical excitation. GJA1-20k deficient mice (generated by a M213L substitution in Gja1) suffer poor electrical coupling between cardiomycytes and arrhythmogenic sudden death two to 4 weeks after their birth. We recently identified that exogenous GJA1-20k expression also mimics the effect of ischemic preconditioning in mouse heart. Furthermore, GJA1-20k localizes to the mitochondrial outer membrane and induces a protective and DRP1 independent form of mitochondrial fission, preserving ATP production and generating less reactive oxygen species (ROS) under metabolic stress, providing powerful protection of myocardium to ischemic insult. In this manuscript, we focus on the detailed roles of GJA1-20k in mitochondria, and its interaction with the actin cytoskeleton.
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影响因子：
9.2
作者：
De Vos, KJ;Allan, VJ;Sheetz, MP
通讯作者：
Sheetz, MP
DOI：
10.1016/j.bbamem.2017.05.018
发表时间：
2018-01
期刊：
Biochimica et biophysica acta. Biomembranes
影响因子：
--
作者：
Epifantseva I;Shaw RM
通讯作者：
Shaw RM
DOI：
10.1152/ajpheart.01278.2008
发表时间：
2009-07-01
影响因子：
4.8
作者：
Kavazis, Andreas N.;Alvarez, Sophie;Powers, Scott K.
通讯作者：
Powers, Scott K.
影响因子：
5.3
作者：
Jheng, Huei-Fen;Tsal, Pei-Jane;Tsai, Yau-Sheng
通讯作者：
Tsai, Yau-Sheng
DOI：
10.1016/j.bbamcr.2018.07.014
发表时间：
2018-10-01
影响因子：
5.1
作者：
Hussain, Afaq;Das Sarma, Subhajit;Das Sarma, Jayasri
通讯作者：
Das Sarma, Jayasri