Torn apart: membrane rupture in muscular dystrophies and associated cardiomyopathies
Jan Lammerding, Richard T. Lee
Jan Lammerding, Richard T. Lee
Published July 2, 2007
Citation Information: J Clin Invest. 2007;117(7):1749-1752. https://doi.org/10.1172/JCI32686.
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Commentary

Torn apart: membrane rupture in muscular dystrophies and associated cardiomyopathies

Abstract

Muscular dystrophies are often caused by mutations in cytoskeletal proteins that render cells more susceptible to strain-induced injury in mechanically active tissues such as skeletal or cardiac muscle. In this issue of the JCI, Han et al. report that dysferlin participates in membrane resealing in cardiomyocytes and that exercise results in increased membrane damage and disturbed cardiac function in dysferlin-deficient mice (see the related article beginning on page 1805). Thus, in addition to repetitive membrane damage, inadequate membrane repair may participate in the pathogenesis of muscular dystrophies and cardiomyopathies.

Authors

Jan Lammerding, Richard T. Lee

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Figure 1

Repetitive mechanical strain causes rupture in the plasma membrane under physiological conditions.

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Repetitive mechanical strain causes rupture in the plasma membrane under...
Mutations that predispose cells to membrane damage or impair the normal repair process cause accumulation of necrotic cells in mechanically active tissue, resulting in muscular dystrophies and cardiomyopathies. Mutations in the nuclear envelope proteins lamin A/C or emerin can decrease the stability of the nuclear lamina and result in nuclear envelope rupture, causing similar muscular dystrophies and cardiomyopathies. In this issue of the JCI, Han et al. (11) report that dysferlin is required for stress-induced membrane repair in cardiomyocytes. While the precise membrane-repair mechanism remains unclear, it is thought that dysferlin-carrying repair vesicles are recruited to the rupture site and fuse with the plasma membrane through interaction with annexins, other dysferlins, and other unknown binding partners (27). LINC, linker of nucleoskeleton and cytoskeleton. Figure adapted with permission from the New England Journal of Medicine (28).