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 Ca2+ increase results in assembly of ESCRTIII 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 Ca2+-dependent accumulation of ESCRTIII-Vps4 complex following large focal injury to the cell membrane and identify the role of ALG-2 as the initiator of sequential ESCRTIII-Vps4 complex assembly that facilitates scission and repair of the injured cell membrane.
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