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.
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: A Al-Haddad; M A Shonn; B Redlich; A Blocker; J K Burkhardt; H Yu; J A Hammer; D G Weiss; W Steffen; G Griffiths; S A Kuznetsov Journal: Mol Biol Cell Date: 2001-09 Impact factor: 4.138
Authors: Steven P Gross; M Carolina Tuma; Sean W Deacon; Anna S Serpinskaya; Amy R Reilein; Vladimir I Gelfand Journal: J Cell Biol Date: 2002-02-25 Impact factor: 10.539
Authors: M Amanda Hartman; Dina Finan; Sivaraj Sivaramakrishnan; James A Spudich Journal: Annu Rev Cell Dev Biol Date: 2011-05-31 Impact factor: 13.827
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