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Nat Commun. 2014 Dec 23;5:5646. doi: 10.1038/ncomms6646.

Mechanism of Ca²⁺-triggered ESCRT assembly and regulation of cell membrane repair.

Author information

1
Children's National Medical Center, Center for Genetic Medicine Research, 111 Michigan Avenue, NW, Washington DC 20010-2970, USA.
2
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.

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.

PMID:
25534348
PMCID:
PMC4333728
DOI:
10.1038/ncomms6646
[Indexed for MEDLINE]
Free PMC Article

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