From the cell membrane to the nucleus: unearthing transport mechanisms for dynein

Bull Math Biol. 2012 Sep;74(9):2032-61. doi: 10.1007/s11538-012-9745-x. Epub 2012 Jul 12.

Abstract

Mutations in the motor protein cytoplasmic dynein have been found to cause Charcot-Marie-Tooth disease, spinal muscular atrophy, and severe intellectual disabilities in humans. In mouse models, neurodegeneration is observed. We sought to develop a novel model which could incorporate the effects of mutations on distance travelled and velocity. A mechanical model for the dynein mediated transport of endosomes is derived from first principles and solved numerically. The effects of variations in model parameter values are analysed to find those that have a significant impact on velocity and distance travelled. The model successfully describes the processivity of dynein and matches qualitatively the velocity profiles observed in experiments.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenosine Triphosphate / metabolism
  • Biological Transport
  • Cell Membrane / metabolism*
  • Cell Nucleus / metabolism*
  • Cytoplasmic Dyneins / metabolism*
  • Endocytosis
  • ErbB Receptors / metabolism
  • Models, Biological*
  • Numerical Analysis, Computer-Assisted

Substances

  • Adenosine Triphosphate
  • ErbB Receptors
  • Cytoplasmic Dyneins