Keratins in Skeletal Muscle: Effects of Altering Expression of Type I/Type II Keratin Pairs

Abstract

Intermediate filaments, a family of fibrillar proteins, are responsible for cell scaffolding and stabilizing the cell against physical stressors, as well as linking organelles within the cell. Their role in skeletal muscle is thought to be critical for maintaining the integrity and function of the cell. Recently, our laboratory identified keratin 8 and 19 in adult skeletal muscle, belonging to the keratin sub-group of intermediate filament proteins. Here, we have identified four additional keratins in skeletal muscle: 7, 18, 23 and 26. These keratin subunits are classified as either type I (K18, K19, K23 and K26) or type II (K7, K8). We examined the effect on muscle of altering expression of either a type I or type II keratin on keratins of the same or opposite type. Our results indicate that some keratins appear to have a preferential binding partner but are capable of forming heterodimers with multiple partners. Furthermore, decreased or increased expression of certain keratins has the ability to not only influence the formation of keratin filaments, but also to cause disruption to the entire intermediate filament cytoskeleton, primarily through formation of aggregates or vacuoles. These findings suggest that keratins play a wider role in skeletal muscle than previously hypothesized, and that abnormal keratin expression may be myopathic.