A mathematical understanding of how cytoplasmic dynein walks on microtubules

Trott, L, Hafezparast, M and Madzvamuse, A (2018) A mathematical understanding of how cytoplasmic dynein walks on microtubules. Royal Society Open Science, 5 (8). p. 171568. ISSN 2054-5703

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Cytoplasmic dynein 1 (hereafter referred to simply as dynein) is a dimeric motor protein that walks and transports intracellular cargos towards the minus end of microtubules. In this article, we formulate, based on physical principles, a mechanical model to describe the stepping behaviour of cytoplasmic dynein walking on microtubules from the cell membrane towards the nucleus. Unlike previous studies on physical models of this nature, we base our formulation on the whole structure of dynein to include the temporal dynamics of the individual subunits such as the cargo ( for example, an endosome, vesicle or bead), two rings of six ATPase domains associated with diverse cellular activities (AAAþ rings) and the microtubule-binding domains which allow dynein to bind to microtubules. This mathematical framework allows us to examine experimental observations on dynein across a wide range of different species, as well as being able to make predictions on the temporal behaviour of the individual components of dynein not currently experimentally measured. Furthermore, we extend the model framework to include backward stepping, variable step size and dwelling. The power of our model is in its predictive nature; first it reflects recent experimental observations that dynein walks on microtubules using a weakly coordinated stepping pattern with predominantly not passing steps. Second, the model predicts that interhead coordination in the ATP cycle of cytoplasmic dynein is important in order to obtain the alternating stepping patterns and long run lengths seen in experiments.

Item Type: Article
Keywords: Cytoplasmic dynein, mathematical modelling
Schools and Departments: School of Life Sciences > Neuroscience
School of Mathematical and Physical Sciences > Mathematics
Subjects: Q Science > Q Science (General)
Q Science > QA Mathematics
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Depositing User: Majid Hafezparast
Date Deposited: 13 Aug 2018 10:34
Last Modified: 18 Feb 2022 15:50
URI: http://sro.sussex.ac.uk/id/eprint/77757

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Project NameSussex Project NumberFunderFunder Ref
InCeM: Research Training Network on Integrated Component Cycling in Epithelial Cell MotilityG1546EUROPEAN UNION642866 - InCeM
New predictive mathematical and computational models in experimental sciencesG1949ROYAL SOCIETYWM160017
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