The palladin/myotilin/myopalladin family of actin-associated scaffolds

Abstract

The dynamic remodeling of the actin cytoskeleton plays a critical role in cellular morphogenesis and cell motility. Actin-associated scaffolds are key to this process, as they recruit cohorts of actin-binding proteins and associated signaling complexes to subcellular sites where remodeling is required. This review is focused on a recently discovered family of three proteins, myotilin, palladin, and myopalladin, all of which function as scaffolds that regulate actin organization. While myotilin and myopalladin are most abundant in skeletal and cardiac muscle, palladin is ubiquitously expressed in the organs of developing vertebrates. Palladin's function has been investigated primarily in the central nervous system and in tissue culture, where it appears to play a key role in cellular morphogenesis. The three family members each interact with specific molecular partners: all three bind to alpha-actinin; in addition, palladin also binds to vasodilator-stimulated phosphoprotein (VASP) and ezrin, myotilin binds to filamin and actin, and myopalladin also binds to nebulin and cardiac ankyrin repeat protein (CARP). Since mutations in myotilin result in two forms of muscle disease, an essential role for this family member in organizing the skeletal muscle sarcomere is implied.