biostudies-literatureBelyy VMedical Research CouncilWellcome TrustNIGMS NIH HHS1018-24https://www.ebi.ac.uk/biostudies/studies/S-EPMC5007201biostudies-literatureUnknown18(9)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 Nature cell biologyThe mammalian dynein-dynactin complex is a strong opponent to kinesin in a tug-of-war competition.PMC5007201MC_UP_A025_1011R01 GM094522WT100387100387Belyy VReimer AECarter APSchlager MAFoster HYildiz AfalseThe mammalian dynein-dynactin complex is a strong opponent to kinesin in a tug-of-war competition.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 2016-01-01T00:00:00Z2016 Sep2026-04-17T15:30:32.678Z2019-03-27T02:23:13ZS-EPMC50072012745481910.1038/ncb3393