title: The mammalian dynein-dynactin complex is a strong opponent to kinesin in a tug-of-war competition.
abstract: Kinesin and dynein motors transport intracellular cargos bidirectionally by pulling them in opposite directions along microtubules, through a process frequently described as a 'tug of war'. While kinesin produces 6 pN of force, mammalian dynein was found to be a surprisingly weak motor (0.5-1.5 pN) in vitro, suggesting that many dyneins are required to counteract the pull of a single kinesin. Mammalian dynein's association with dynactin and Bicaudal-D2 (BICD2) activates its processive motility, but it was unknown how this affects dynein's force output. Here, we show that formation of the dynein-dynactin-BICD2 (DDB) complex increases human dynein's force production to 4.3 pN. An in vitro tug-of-war assay revealed that a single DDB successfully resists a single kinesin. Contrary to previous reports, the clustering of many dyneins is not required to win the tug of war. Our work reveals the key role of dynactin and a cargo adaptor protein in shifting the balance of forces between dynein and kinesin motors during intracellular transport.
authors.affiliation: Biophysics Graduate Group, University of California at Berkeley, Berkeley, California 94720, USA.
authors.forename: Vladislav
authors.initials: V
authors.lastname: Belyy
authors.affiliation: Medical Research Council Laboratory of Molecular Biology, Division of Structural Studies, Francis Crick Avenue, Cambridge CB2 0QH, UK.
authors.forename: Max A
authors.initials: MA
authors.lastname: Schlager
authors.affiliation: Medical Research Council Laboratory of Molecular Biology, Division of Structural Studies, Francis Crick Avenue, Cambridge CB2 0QH, UK.
authors.forename: Helen
authors.initials: H
authors.lastname: Foster
authors.affiliation: Biophysics Graduate Group, University of California at Berkeley, Berkeley, California 94720, USA.
authors.forename: Armando E
authors.initials: AE
authors.lastname: Reimer
authors.affiliation: Medical Research Council Laboratory of Molecular Biology, Division of Structural Studies, Francis Crick Avenue, Cambridge CB2 0QH, UK.
authors.forename: Andrew P
authors.initials: AP
authors.lastname: Carter
authors.affiliation: Department of Physics, University of California at Berkeley, Berkeley, California 94720, USA.|Department of Cellular and Molecular Biology, University of California at Berkeley, Berkeley, California 94720, USA.
authors.forename: Ahmet
authors.initials: A
authors.lastname: Yildiz
mesh_terms: D000818:Animals; D001692:Biological Transport; D003599:Cytoskeleton / Q000378:metabolism; D000072159:Dynactin Complex / Q000378:metabolism*; D004398:Dyneins / Q000378:metabolism*; D006801:Humans; D016547:Kinesins / Q000378:metabolism*; D008322:Mammals; D008954:Models, Biological
chemical_list: D000072159:Dynactin Complex; D004398:Dyneins; D016547:Kinesins