How Actin Tracks Affect Myosin Motors.

Cellular organization through cytoskeletal trafficking is a process of fundamental importance. Highly specialized systems evolved that enable motors to identify and select the optimal tracks for motility. In this chapter, we examine the profound effect of actin filament networks on myosin motility patterns. We argue that the myosin classes have adaptations that allow them to detect local structural and chemical cues on actin. These cues are often arranged in a coherent manner on actin filament networks, allowing for directed transport over long distances. We identify a number of potentially important cues, ranging from the biochemical states of actin subunits all the way to multi-filament networks and bundles.

Actin age orchestrates myosin-5 and myosin-6 run lengths.

Unlike a static and immobile skeleton, the actin cytoskeleton is a highly dynamic network of filamentous actin (F-actin) polymers that continuously turn over. In addition to generating mechanical forces and sensing mechanical deformation, dynamic F-actin networks serve as cellular tracks for myosin motor traffic. However, much of our mechanistic understanding of processive myosins comes from in vitro studies in which motility was studied on pre-assembled and artificially stabilized, static F-actin tracks. In this work, we examine the role of actin dynamics in single-molecule myosin motility using assembling F-actin and two highly processive motors, myosin-5 and myosin-6. These two myosins have distinct functions in the cell and travel in opposite directions along actin filaments [1-3]. Myosin-5 walks toward the barbed ends of F-actin, traveling to sites of actin polymerization at the cell periphery [4]. Myosin-6 walks toward the pointed end of F-actin [5], traveling toward the cell center along older segments of the actin filament. We find that myosin-5 takes 1.3- to 1.5-fold longer runs on ADP•Pi (young) F-actin, whereas myosin-6 takes 1.7- to 3.6-fold longer runs along ADP (old) F-actin. These results suggest that conformational differences between ADP•Pi and ADP F-actin tailor these myosins to walk farther toward their preferred actin filament end. Taken together, these experiments define a new mechanism by which myosin traffic may sort to different F-actin networks depending on filament age.