Scheffer Luana L, Sreetama Sen Chandra, Sharma Nimisha, Medikayala Sushma, Brown Kristy J, Defour Aurelia, Jaiswal Jyoti K
Children's National Medical Center, Center for Genetic Medicine Research, 111 Michigan Avenue, NW, Washington DC 20010-2970, USA.
1] Children's National Medical Center, Center for Genetic Medicine Research, 111 Michigan Avenue, NW, Washington DC 20010-2970, USA [2] Department of Integrative Systems Biology, George Washington University School of Medicine and Health Sciences, Washington DC, USA.
Nat Commun. 2014 Dec 23;5:5646. doi: 10.1038/ncomms6646.
In muscle and other mechanically active tissue, cell membranes are constantly injured, and their repair depends on the injury-induced increase in cytosolic calcium. Here, we show that injury-triggered Ca(2+) increase results in assembly of ESCRT III and accessory proteins at the site of repair. This process is initiated by the calcium-binding protein-apoptosis-linked gene (ALG)-2. ALG-2 facilitates accumulation of ALG-2-interacting protein X (ALIX), ESCRT III and Vps4 complex at the injured cell membrane, which in turn results in cleavage and shedding of the damaged part of the cell membrane. Lack of ALG-2, ALIX or Vps4B each prevents shedding, and repair of the injured cell membrane. These results demonstrate Ca(2+)-dependent accumulation of ESCRT III-Vps4 complex following large focal injury to the cell membrane and identify the role of ALG-2 as the initiator of sequential ESCRT III-Vps4 complex assembly that facilitates scission and repair of the injured cell membrane.
在肌肉和其他机械活性组织中，细胞膜不断受到损伤，其修复依赖于损伤诱导的胞质钙增加。在此，我们表明损伤引发的Ca(2+)增加导致ESCRT III及其辅助蛋白在修复部位组装。这一过程由钙结合蛋白——凋亡相关基因（ALG）-2启动。ALG-2促进ALG-2相互作用蛋白X（ALIX）、ESCRT III和Vps4复合物在受损细胞膜上的积累，进而导致细胞膜受损部分的切割和脱落。缺乏ALG-2、ALIX或Vps4B均会阻止脱落以及受损细胞膜的修复。这些结果证明了细胞膜受到大面积局灶性损伤后ESCRT III-Vps4复合物的钙依赖性积累，并确定了ALG-2作为ESCRT III-Vps4复合物顺序组装启动子的作用，该组装促进了受损细胞膜的切割和修复。
