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Nat Cell Biol. 2016 Sep;18(9):1018-24. doi: 10.1038/ncb3393. Epub 2016 Jul 25.

The mammalian dynein-dynactin complex is a strong opponent to kinesin in a tug-of-war competition.

Author information

1
Biophysics Graduate Group, University of California at Berkeley, Berkeley, California 94720, USA.
2
Medical Research Council Laboratory of Molecular Biology, Division of Structural Studies, Francis Crick Avenue, Cambridge CB2 0QH, UK.
3
Department of Physics, University of California at Berkeley, Berkeley, California 94720, USA.
4
Department of Cellular and Molecular Biology, University of California at Berkeley, Berkeley, California 94720, USA.

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.

PMID:
27454819
PMCID:
PMC5007201
DOI:
10.1038/ncb3393
[Indexed for MEDLINE]
Free PMC Article

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