1. Mechanism of Ca²⁺-triggered ESCRT assembly and regulation of cell membrane repair.
- Author
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Scheffer LL, Sreetama SC, Sharma N, Medikayala S, Brown KJ, Defour A, and Jaiswal JK
- Subjects
- ATPases Associated with Diverse Cellular Activities, Adenosine Triphosphatases genetics, Animals, Apoptosis Regulatory Proteins genetics, Calcium-Binding Proteins genetics, Cell Cycle Proteins genetics, Cell Membrane enzymology, Cell Membrane genetics, Endosomal Sorting Complexes Required for Transport genetics, Humans, Mice, Myoblasts enzymology, Myoblasts metabolism, Protein Multimerization, Vacuolar Proton-Translocating ATPases genetics, Adenosine Triphosphatases metabolism, Apoptosis Regulatory Proteins metabolism, Calcium metabolism, Calcium-Binding Proteins metabolism, Cell Cycle Proteins metabolism, Cell Membrane metabolism, Endosomal Sorting Complexes Required for Transport metabolism, Vacuolar Proton-Translocating ATPases metabolism
- Abstract
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.
- Published
- 2014
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