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

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

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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, U.S. Gov't, Non-P.H.S.
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Biological Transport
  • Cytoskeleton / metabolism
  • Dynactin Complex / metabolism*
  • Dyneins / metabolism*
  • Humans
  • Kinesin / metabolism*
  • Mammals
  • Models, Biological

Substances

  • Dynactin Complex
  • Dyneins
  • Kinesin