title: Actin age orchestrates myosin-5 and myosin-6 run lengths.
abstract: 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.
authors.affiliation: Department of Molecular Genetics and Cell Biology, The University of Chicago, 929 E. 57th Street, Chicago, IL 60637, USA.
authors.forename: Dennis
authors.initials: D
authors.lastname: Zimmermann
authors.affiliation: Department of Biochemistry and Molecular Biology, The University of Chicago, 929 E. 57th Street, Chicago, IL 60637, USA.
authors.forename: Alicja
authors.initials: A
authors.lastname: Santos
authors.affiliation: Department of Molecular Genetics and Cell Biology, The University of Chicago, 929 E. 57th Street, Chicago, IL 60637, USA; Department of Biochemistry and Molecular Biology, The University of Chicago, 929 E. 57th Street, Chicago, IL 60637, USA. Electronic address: drkovar@uchicago.edu.
authors.forename: David R
authors.initials: DR
authors.lastname: Kovar
authors.affiliation: Department of Biochemistry and Molecular Biology, The University of Chicago, 929 E. 57th Street, Chicago, IL 60637, USA. Electronic address: rrock@uchicago.edu.
authors.forename: Ronald S
authors.initials: RS
authors.lastname: Rock
mesh_terms: D008841:Actin Cytoskeleton / Q000378:metabolism*; D000199:Actins / Q000378:metabolism*; D000818:Animals; D009218:Myosins / Q000378:metabolism*; D011817:Rabbits
chemical_list: D000199:Actins; D009218:Myosins