title: Motor number controls cargo switching at actin-microtubule intersections in vitro.
abstract: BACKGROUND
  Cellular activities such as endocytosis and secretion require that cargos actively switch between the microtubule (MT) and actin filament (AF) networks. Cellular studies suggest that switching may involve a tug of war or coordinate regulation of MT- and AF-based motor function.
  
  
  RESULTS
  To test the hypothesis that motor number can be used to direct the outcome of a tug-of-war process, we reconstituted cargo switching at MT-AF intersections in a minimal system with purified myosin V and dynein-dynactin motors bound to beads. Beads containing both motors often paused at the intersections and rotated about an axis perpendicular to both filaments, suggesting that competing motors apply a torque on their cargo. Force measurements showed that motor forces scale with the number of engaged myosin V and dynein-dynactin motors. Whether beads remained on a MT or AF or switched to the alternate track was determined by which set of motors collectively produced greater force. Passing and switching probabilities were similar whether the bead approached an intersection on either a MT or an AF. Beads with a force ratio near unity had approximately equal probabilities of exiting on the MT, exiting on the AF, or remaining stalled at the intersection. A simple statistical model quantitatively describes the relationship between switching probability and motor number.
  
  
  CONCLUSIONS
  Cargo switching can be tuned via combinations of 1-4 myosin V and 1-4 dynein-dynactin engaged motors through a simple force-mediated mechanism.
authors.affiliation: Pennsylvania Muscle Institute and the Department of Physiology, University of Pennsylvania School of Medicine, Philadelphia, PA 19104-6085, USA.
authors.forename: Harry W
authors.initials: HW
authors.lastname: Schroeder
authors.forename: Chris
authors.initials: C
authors.lastname: Mitchell
authors.forename: Henry
authors.initials: H
authors.lastname: Shuman
authors.forename: Erika L F
authors.initials: EL
authors.lastname: Holzbaur
authors.forename: Yale E
authors.initials: YE
authors.lastname: Goldman
mesh_terms: D008841:Actin Cytoskeleton / Q000378:metabolism* / Q000648:ultrastructure; D000818:Animals; D001692:Biological Transport / Q000502:physiology*; D002417:Cattle; D002645:Chickens; D000072159:Dynactin Complex; D004398:Dyneins / Q000378:metabolism; D008869:Microtubule-Associated Proteins / Q000378:metabolism; D008870:Microtubules / Q000378:metabolism* / Q000648:ultrastructure; D008954:Models, Biological; D020409:Molecular Motor Proteins / Q000378:metabolism*; D024701:Myosin Type V / Q000378:metabolism; D011817:Rabbits; D012399:Rotation; D013314:Stress, Mechanical
chemical_list: D000072159:Dynactin Complex; D008869:Microtubule-Associated Proteins; D020409:Molecular Motor Proteins; D024701:Myosin Type V; D004398:Dyneins
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