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 is a molecular motor implicated in many processes, and it likely associates with a variety of cargoes that specify its functions. Although it is critical to Drosophila development, little is known about its cellular roles. To reveal its involvement in specific pathways, we sought to identify the binding partners of Drosophila myosin VI. We used affinity chromatography and mass spectrometry to discover interacting proteins, which we tested for direct binding. Using this approach, we found that the microtubuleassociated protein Cornetto bound myosin VI, and we demonstrated a role for both in secretion of the lipidated morphogen Hedgehog. We also identified a number of other binding proteins, and further characterization of their interactions with myosin VI will advance our understanding of the roles of these complexes in cellular and developmental processes. Thus, our method has provided us the means to gain valuable insight into the multifaceted roles of a motor protein in vivo.unconventional myosins | cytoskeleton | trafficking M yosins comprise a superfamily of actin-based motor proteins involved in a variety of processes (1). On the molecular scale, significant progress has been made in recent years toward understanding their mechanical properties (2, 3). On the organismal scale, it is also clear that they are important for the development and function of tissues and organs (4-6). Yet for many of these proteins, there is little data explaining their roles on the cellular level. As functions of motor proteins are thought to be determined by the types of cargoes they transport (7), an important step in furthering our understanding of motors' functions is identifying the proteins and organelles with which they interact (8).Toward this goal, we have focused on myosin VI, which participates in a wide range of processes such as vesicle trafficking and maintenance of stereocilia for mammalian hearing (9). Its broad utilization in higher organisms is perhaps due to its unique directionality toward the minus ends of actin filaments, unlike all other studied myosins (reviewed in ref. 10 and others). Although yeast two-hybrid screens and other approaches have made progress toward identifying some myosin VI cargoes (11), less is known about the molecular details of how myosin VI complexes function in vivo. Such information is particularly lacking about this protein in Drosophila, despite its significance in fly development.Depletion of Drosophila myosin VI (Jaguar; referred to as M6 throughout) protein levels, expression of a dominant negative M6 truncation, or injection of a function-blocking M6 antibody produces a variety of phenotypes that depend on the stage and tissue targeted (12). These data have revealed roles for M6 in pseudocleavage furrow formation in the syncytium (13), dorsal closure later in embryogenesis (14), and spermatogenesis in the adult male (15), among other processes (16).Though its importance is evident, it is unclear what M6 contributes as a motor protein to developmental events, because...
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.
hi@scite.ai
10624 S. Eastern Ave., Ste. A-614
Henderson, NV 89052, USA
Copyright © 2024 scite LLC. All rights reserved.
Made with 💙 for researchers
Part of the Research Solutions Family.