Force-induced Bidirectional Stepping of Cytoplasmic Dynein

Cell. 2007 Nov 30;131(5):952-65. doi: 10.1016/j.cell.2007.10.016.

Abstract

Cytoplasmic dynein is a minus-end-directed microtubule motor whose mechanism of movement remains poorly understood. Here, we use optical tweezers to examine the force-dependent stepping behavior of yeast cytoplasmic dynein. We find that dynein primarily advances in 8 nm increments but takes other sized steps (4-24 nm) as well. An opposing force induces more frequent backward stepping by dynein, and the motor walks backward toward the microtubule plus end at loads above its stall force of 7 pN. Remarkably, in the absence of ATP, dynein steps processively along microtubules under an external load, with less force required for minus-end- than for plus-end-directed movement. This nucleotide-independent walking reveals that force alone can drive repetitive microtubule detachment-attachment cycles of dynein's motor domains. These results suggest a model for how dynein's two motor domains coordinate their activities during normal processive motility and provide new clues for understanding dynein-based motility in living cells.

Publication types

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

MeSH terms

  • Adenosine Triphosphate / metabolism
  • Biological Transport, Active
  • Biomechanical Phenomena
  • Cytoplasm / metabolism
  • Dyneins / chemistry
  • Dyneins / metabolism
  • Dyneins / physiology*
  • Hydrolysis
  • Models, Biological
  • Protein Structure, Tertiary / physiology
  • Saccharomyces cerevisiae

Substances

  • Adenosine Triphosphate
  • Dyneins