Metavinculin: New insights into functional properties of a muscle adhesion protein

Abstract

Metavinculin is a muscle-specific splice variant of the ubiquitously expressed cytoskeletal adaptor protein vinculin. Both proteins are thought to be co-expressed in all muscle types where they co-localize to microfilament-associated adhesion sites. It has been shown that a metavinculin-specific insertion of 68 amino acids alters the biochemical properties of the five-helix bundle in the tail domain. Here, we demonstrate that the metavinculin-specific helix H1' plays an important role for protein stability of the tail domain, since a point mutation in this helix, R975W, which is associated with the occurrence of dilated cardiomyopathy in man, further decreases thermal stability of the metavinculin tail domain. In striated muscle progenitor cells (myoblasts), both, metavinculin and the R975W mutant show significantly reduced, albeit distinctive residency and exchange rates in adhesion sites as compared to vinculin. In contrast to previous studies, we show that metavinculin is localized in a muscle fiber type-dependent fashion to the costameres of striated muscle, reflecting the individual metabolic and physiological status of a given muscle fiber. Metavinculin expression is highest in fast, glycolytic muscle fibers and virtually absent in M. diaphragmaticus, a skeletal muscle entirely lacking fast, glycolytic fibers. In summary, our data suggest that metavinculin enrichment in attachment sites of muscle cells leads to higher mechanical stability of adhesion complexes allowing for greater shear force resistance.