From the cell membrane to the nucleus: unearthing transport mechanisms for dynein.
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.
School of Mathematical and Physical Sciences, Department of Mathematics, University of Sussex, Pev III, 5C15, Brighton, BN1 9QH, UK.
Laurie
L
Crossley
Caroline A
CA
Garrett
Majid
M
Hafezparast
Anotida
A
Madzvamuse
D000255:Adenosine Triphosphate / Q000378:metabolism; D001692:Biological Transport; D002462:Cell Membrane / Q000378:metabolism*; D002467:Cell Nucleus / Q000378:metabolism*; D056445:Cytoplasmic Dyneins / Q000378:metabolism*; D004705:Endocytosis; D066246:ErbB Receptors / Q000378:metabolism; D008954:Models, Biological; D009716:Numerical Analysis, Computer-Assisted
D000255:Adenosine Triphosphate; D066246:ErbB Receptors; D056445:Cytoplasmic Dyneins