Load-induced enhancement of Dynein force production by LIS1-NudE in vivo and in vitro

Nat Commun. 2016 Aug 4:7:12259. doi: 10.1038/ncomms12259.

Abstract

Most sub-cellular cargos are transported along microtubules by kinesin and dynein molecular motors, but how transport is regulated is not well understood. It is unknown whether local control is possible, for example, by changes in specific cargo-associated motor behaviour to react to impediments. Here we discover that microtubule-associated lipid droplets (LDs) in COS1 cells respond to an optical trap with a remarkable enhancement in sustained force production. This effect is observed only for microtubule minus-end-moving LDs. It is specifically blocked by RNAi for the cytoplasmic dynein regulators LIS1 and NudE/L (Nde1/Ndel1), but not for the dynactin p150(Glued) subunit. It can be completely replicated using cell-free preparations of purified LDs, where duration of LD force production is more than doubled. These results identify a novel, intrinsic, cargo-associated mechanism for dynein-mediated force adaptation, which should markedly improve the ability of motor-driven cargoes to overcome subcellular obstacles.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Animals
  • Biomechanical Phenomena
  • COS Cells
  • Carrier Proteins / metabolism*
  • Chlorocebus aethiops
  • Drosophila melanogaster
  • Dyneins / metabolism*
  • Lipid Droplets / metabolism
  • Microtubule-Associated Proteins / metabolism*
  • Models, Biological
  • Motion

Substances

  • Carrier Proteins
  • Microtubule-Associated Proteins
  • Dyneins