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From the Cell Membrane to the Nucleus: Unearthing Transport Mechanisms for Dynein

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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.

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Acknowledgements

LC was supported by a University of Sussex Junior Research Fellowship 2011. AM would like to acknowledge grant financial support from the LMS (R4P2), EPSRC (EP/H020349/1), the Royal Society Travel grant (R4K1), the Royal Society Research Grant (R4N9), and the British Council through its UK-US New Partnership Fund as part of the Strategic Alliances and Partnerships strand of the Prime Minister’s Initiative for International Education 2 (PMI2). MH and CG would like to acknowledge financial support from the BBSRC (BB/D526861/1).

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Authors and Affiliations

  1. School of Mathematical and Physical Sciences, Department of Mathematics, University of Sussex, Pev III, 5C15, Brighton, BN1 9QH, UK

    Laurie Crossley & Anotida Madzvamuse

  2. School of Life Sciences, University of Sussex, John Maynard Smith Building, Brighton, BN1 9QG, UK

    Caroline A. Garrett & Majid Hafezparast

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  1. Laurie Crossley
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  2. Caroline A. Garrett
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  4. Anotida Madzvamuse
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Correspondence to Anotida Madzvamuse.

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Crossley, L., Garrett, C.A., Hafezparast, M. et al. From the Cell Membrane to the Nucleus: Unearthing Transport Mechanisms for Dynein. Bull Math Biol 74, 2032–2061 (2012). https://doi.org/10.1007/s11538-012-9745-x

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