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A mathematical understanding of how cytoplasmic dynein walks on microtubules

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posted on 2023-06-09, 14:30 authored by L Trott, Majid HafezparastMajid Hafezparast, Anotida MadzvamuseAnotida Madzvamuse
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.

Funding

New predictive mathematical and computational models in experimental sciences; G1949; ROYAL SOCIETY; WM160017

Unravelling new mathematics for 3D cell migration; G1438; LEVERHULME TRUST; RPG-2014-149

InCeM: Research Training Network on Integrated Component Cycling in Epithelial Cell Motility; G1546; EUROPEAN UNION; 642866 - InCeM

History

Publication status

  • Published

File Version

  • Published version

Journal

Royal Society Open Science

ISSN

2054-5703

Publisher

Royal Society, The

Issue

8

Volume

5

Page range

171568

Department affiliated with

  • Neuroscience Publications

Full text available

  • Yes

Peer reviewed?

  • Yes

Legacy Posted Date

2018-08-13

First Open Access (FOA) Date

2018-08-13

First Compliant Deposit (FCD) Date

2018-08-09

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