Principles of Unconventional Myosin Function and Targeting

Abstract

Unconventional myosins are a superfamily of actin-based motors implicated in diverse cellular processes. In recent years, much progress has been made in describing their biophysical properties, and headway has been made into analyzing their cellular functions. Here, we focus on the principles that guide in vivo motor function and targeting to specific cellular locations. Rather than describe each motor comprehensively, we outline the major themes that emerge from research across the superfamily and use specific examples to illustrate each. In presenting the data in this format, we seek to identify open questions in each field as well as to point out commonalities between them. To advance our understanding of myosins’ roles in vivo, clearly we must identify their cellular cargoes and the protein complexes that regulate motor attachment to fully appreciate their functions on the cellular and developmental levels.

Myosin VI and its cargo adaptors – linking endocytosis and autophagy

“…The conventional myosins, which comprise the non-muscle myosin II family and the skeletal, cardiac and smooth muscle myosins, assemble to form bipolar filaments that mediate sliding and crosslinking of actin filaments to generate contractility and tension. By contrast, unconventional myosins do not form filaments but, rather, function as either monomeric or dimeric cargo transporters, regulators of actin organisation, adjustable tethers for organelles, and/or as loaddependent tension sensors (Bloemink and Geeves, 2011;Hartman et al, 2011). The precise cellular roles of the different classes of unconventional myosins are mainly due to their divergent cargobinding tail regions that mediate distinct interactions for targeting to various subcellular locations.…”

Myosin VIIA regulates microvillus morphogenesis and interacts with cadherin Cad99C in Drosophila oogenesis

“…In particular, myosin motor proteins, which bind to and travel along actin filaments, control multiple processes in microvilli and stereocilia. Myosins have been implicated in transporting, anchoring and concentrating protein complexes and membrane vesicles, in exerting tension force on the plasma membrane and in influencing the structure of actin networks (reviewed by Krendel and Mooseker, 2005;Nambiar et al, 2010;Schwander et al, 2010;Hartman et al, 2011).…”

Myosin-X: a MyTH-FERM myosin at the tips of filopodia

“…The myosins are a superfamily of actin-based motor proteins that have crucial roles in cellular and organismal physiology (Hartman et al, 2011). Myosins typically consist of a head domain that can bind to actin filaments and generate force, a neck domain that provides binding sites for myosin light chains, and a tail that endows specific properties, such as dimerization and binding to cargo.…”