title: Engineered Tug-of-War Between Kinesin and Dynein Controls Direction of Microtubule Based Transport In Vivo.
abstract: Bidirectional transport of membrane organelles along microtubules (MTs) is driven by plus-end directed kinesins and minus-end directed dynein bound to the same cargo. Activities of opposing MT motors produce bidirectional movement of membrane organelles and cytoplasmic particles along MT transport tracks. Directionality of MT-based transport might be controlled by a protein complex that determines which motor type is active at any given moment of time, or determined by the outcome of a tug-of-war between MT motors dragging cargo organelles in opposite directions. However, evidence in support of each mechanisms of regulation is based mostly on the results of theoretical analyses or indirect experimental data. Here, we test whether the direction of movement of membrane organelles in vivo can be controlled by the tug-of-war between opposing MT motors alone, by attaching a large number of kinesin-1 motors to organelles transported by dynein to minus-ends of MTs. We find that recruitment of kinesin significantly reduces the length and velocity of minus-end-directed dynein-dependent MT runs, leading to a reversal of the overall direction of dynein-driven organelles in vivo. Therefore, in the absence of external regulators tug-of-war between opposing MT motors alone is sufficient to determine the directionality of MT transport in vivo.
authors: R.D.Berlin Center for Cell Analysis and Modeling, and Department of Cell Biology, UConn Health, 400 Farmington Avenue, Farmington, CT 06030-6406, USA.
authors: Karim
authors: K
authors: Rezaul
authors: R.D.Berlin Center for Cell Analysis and Modeling, and Department of Cell Biology, UConn Health, 400 Farmington Avenue, Farmington, CT 06030-6406, USA.
authors: Dipika
authors: D
authors: Gupta
authors: R.D.Berlin Center for Cell Analysis and Modeling, and Department of Cell Biology, UConn Health, 400 Farmington Avenue, Farmington, CT 06030-6406, USA.
authors: Irina
authors: I
authors: Semenova
authors: R.D.Berlin Center for Cell Analysis and Modeling, and Department of Cell Biology, UConn Health, 400 Farmington Avenue, Farmington, CT 06030-6406, USA.|Current address: Quantitative Biology Center, RIKEN, Osaka 565-0874, Japan.
authors: Kazuho
authors: K
authors: Ikeda
authors: Department of Biological Sciences, Virginia Polytechnic Institute and State University, Blacksburg, VA 24061-0406, USA.
authors: Pavel
authors: P
authors: Kraikivski
authors: R.D.Berlin Center for Cell Analysis and Modeling, and Department of Cell Biology, UConn Health, 400 Farmington Avenue, Farmington, CT 06030-6406, USA.
authors: Ji
authors: J
authors: Yu
authors: R.D.Berlin Center for Cell Analysis and Modeling, and Department of Cell Biology, UConn Health, 400 Farmington Avenue, Farmington, CT 06030-6406, USA.
authors: Ann
authors: A
authors: Cowan
authors: Department of Mathematics and Statistics, University of Nevada-Reno, Reno, NV 89557, USA.
authors: Ilya
authors: I
authors: Zaliapin
authors: R.D.Berlin Center for Cell Analysis and Modeling, and Department of Cell Biology, UConn Health, 400 Farmington Avenue, Farmington, CT 06030-6406, USA.
authors: Vladimir
authors: V
authors: Rodionov
mesh_terms: D000818:Animals; D004398:Dyneins / Q000378:metabolism*; D006801:Humans; D016547:Kinesins / Q000378:metabolism*; D008870:Microtubules / Q000378:metabolism*; D021381:Protein Transport
chemical_list: D004398:Dyneins; D016547:Kinesins
keywords: dynein; intracellular transport; kinesin; melanophore; pigment granule