A mathematical understanding of how cytoplasmic dynein walks on microtubules
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 cytopla...
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| Format: | Article |
| Language: | English |
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The Royal Society
2018-01-01
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| Series: | Royal Society Open Science |
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| Online Access: | https://royalsocietypublishing.org/doi/pdf/10.1098/rsos.171568 |
| _version_ | 1819173590329720832 |
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| author | L. Trott M. Hafezparast A. Madzvamuse |
| author_facet | L. Trott M. Hafezparast A. Madzvamuse |
| author_sort | L. Trott |
| collection | DOAJ |
| description | 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 (AAA+ 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. |
| first_indexed | 2024-12-22T20:25:30Z |
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| id | doaj.art-323320a362fb4e87ab9bf4228795ac65 |
| institution | Directory Open Access Journal |
| issn | 2054-5703 |
| language | English |
| last_indexed | 2024-12-22T20:25:30Z |
| publishDate | 2018-01-01 |
| publisher | The Royal Society |
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| series | Royal Society Open Science |
| spelling | doaj.art-323320a362fb4e87ab9bf4228795ac652022-12-21T18:13:45ZengThe Royal SocietyRoyal Society Open Science2054-57032018-01-015810.1098/rsos.171568171568A mathematical understanding of how cytoplasmic dynein walks on microtubulesL. TrottM. HafezparastA. MadzvamuseCytoplasmic 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 (AAA+ 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.https://royalsocietypublishing.org/doi/pdf/10.1098/rsos.171568motor proteincytoplasmic dyneinmicrotubuleendocytosisintracellular transport model |
| spellingShingle | L. Trott M. Hafezparast A. Madzvamuse A mathematical understanding of how cytoplasmic dynein walks on microtubules Royal Society Open Science motor protein cytoplasmic dynein microtubule endocytosis intracellular transport model |
| title | A mathematical understanding of how cytoplasmic dynein walks on microtubules |
| title_full | A mathematical understanding of how cytoplasmic dynein walks on microtubules |
| title_fullStr | A mathematical understanding of how cytoplasmic dynein walks on microtubules |
| title_full_unstemmed | A mathematical understanding of how cytoplasmic dynein walks on microtubules |
| title_short | A mathematical understanding of how cytoplasmic dynein walks on microtubules |
| title_sort | mathematical understanding of how cytoplasmic dynein walks on microtubules |
| topic | motor protein cytoplasmic dynein microtubule endocytosis intracellular transport model |
| url | https://royalsocietypublishing.org/doi/pdf/10.1098/rsos.171568 |
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