Kevin Campell and fellow University of Iowa researchers have shown that a protein known as dysferlin plays a critical role in repairing the plasma membranes of cardiac muscle cells that are torn as a result of strain-induced injury.
Inadequate cell membrane repair may be involved in heart failure and muscular dystrophy. Their results appear in the July 2 issue of the Journal of Clinical Investigation.
Given the considerable shape changes that skeletal and heart muscle undergo as part of their natural function, it?s remarkable that muscle cells just don?t tear apart. In fact, cell membrane rupture occurs frequently under normal conditions but to prevent cell death cells have developed mechanisms to reseal ruptured membranes. In this issue of the JCI, Campbell et al. observed that membrane repair is impaired in cardiac muscle cells that lack the protein dysferlin and that stress exercise was sufficient to disturb normal cardiac function in dysferlin-deficient mice. Cardiac damage was even more severe in mice bred by crossing dysferlin-deficient and dystrophin-deficient mice. Lack of dystrophin is involved in muscular dystrophy. While the precise 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 proteins known as annexins.
In an accompanying commentary, Jan Lammerding and Richard Lee from Harvard Medical School discuss these results and how mutations that predispose cells to membrane damage or impair the normal repair process cause the accumulation of dying cells in mechanically active tissues, resulting in muscular dystrophies and cardiomyopathy. The discovery of alternative, better-tolerated drugs that can drive the membrane repair process would represent a significant advance.
TITLE: Dysferlin-mediated membrane repair protects the heart from stress-induced left ventricular injury