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.
Publication types
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Research Support, N.I.H., Extramural
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Research Support, Non-U.S. Gov't
MeSH terms
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ATPases Associated with Diverse Cellular Activities
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Adenosine Triphosphatases / genetics
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Adenosine Triphosphatases / metabolism*
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Animals
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Apoptosis Regulatory Proteins / genetics
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Apoptosis Regulatory Proteins / metabolism*
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Calcium / metabolism*
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Calcium-Binding Proteins / genetics
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Calcium-Binding Proteins / metabolism*
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Cell Cycle Proteins / genetics
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Cell Cycle Proteins / metabolism*
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Cell Membrane / enzymology
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Cell Membrane / genetics
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Cell Membrane / metabolism*
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Endosomal Sorting Complexes Required for Transport / genetics
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Endosomal Sorting Complexes Required for Transport / metabolism*
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Humans
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Mice
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Myoblasts / enzymology
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Myoblasts / metabolism
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Protein Multimerization
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Vacuolar Proton-Translocating ATPases / genetics
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Vacuolar Proton-Translocating ATPases / metabolism*
Substances
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Apoptosis Regulatory Proteins
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Calcium-Binding Proteins
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Cell Cycle Proteins
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Endosomal Sorting Complexes Required for Transport
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PDCD6 protein, human
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PDCD6IP protein, human
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Adenosine Triphosphatases
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Vacuolar Proton-Translocating ATPases
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ATPases Associated with Diverse Cellular Activities
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VPS4A protein, human
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VPS4B protein, human
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Calcium