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Periodic propagating waves coordinate RhoGTPase network dynamics at the leading and trailing edges during cell migration
Migrating cells need to coordinate distinct leading and trailing edge dynamics but the underlying mechanisms are unclear. Here, we combine experiments and mathematical modeling to elaborate the minimal autonomous biochemical machinery necessary and sufficient for this dynamic coordination and cell m...
Autores principales: | , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
eLife Sciences Publications, Ltd
2020
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7380942/ https://www.ncbi.nlm.nih.gov/pubmed/32705984 http://dx.doi.org/10.7554/eLife.58165 |
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author | Bolado-Carrancio, Alfonso Rukhlenko, Oleksii S Nikonova, Elena Tsyganov, Mikhail A Wheeler, Anne Garcia-Munoz, Amaya Kolch, Walter von Kriegsheim, Alex Kholodenko, Boris N |
author_facet | Bolado-Carrancio, Alfonso Rukhlenko, Oleksii S Nikonova, Elena Tsyganov, Mikhail A Wheeler, Anne Garcia-Munoz, Amaya Kolch, Walter von Kriegsheim, Alex Kholodenko, Boris N |
author_sort | Bolado-Carrancio, Alfonso |
collection | PubMed |
description | Migrating cells need to coordinate distinct leading and trailing edge dynamics but the underlying mechanisms are unclear. Here, we combine experiments and mathematical modeling to elaborate the minimal autonomous biochemical machinery necessary and sufficient for this dynamic coordination and cell movement. RhoA activates Rac1 via DIA and inhibits Rac1 via ROCK, while Rac1 inhibits RhoA through PAK. Our data suggest that in motile, polarized cells, RhoA–ROCK interactions prevail at the rear, whereas RhoA-DIA interactions dominate at the front where Rac1/Rho oscillations drive protrusions and retractions. At the rear, high RhoA and low Rac1 activities are maintained until a wave of oscillatory GTPase activities from the cell front reaches the rear, inducing transient GTPase oscillations and RhoA activity spikes. After the rear retracts, the initial GTPase pattern resumes. Our findings show how periodic, propagating GTPase waves coordinate distinct GTPase patterns at the leading and trailing edge dynamics in moving cells. |
format | Online Article Text |
id | pubmed-7380942 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2020 |
publisher | eLife Sciences Publications, Ltd |
record_format | MEDLINE/PubMed |
spelling | pubmed-73809422020-07-27 Periodic propagating waves coordinate RhoGTPase network dynamics at the leading and trailing edges during cell migration Bolado-Carrancio, Alfonso Rukhlenko, Oleksii S Nikonova, Elena Tsyganov, Mikhail A Wheeler, Anne Garcia-Munoz, Amaya Kolch, Walter von Kriegsheim, Alex Kholodenko, Boris N eLife Cell Biology Migrating cells need to coordinate distinct leading and trailing edge dynamics but the underlying mechanisms are unclear. Here, we combine experiments and mathematical modeling to elaborate the minimal autonomous biochemical machinery necessary and sufficient for this dynamic coordination and cell movement. RhoA activates Rac1 via DIA and inhibits Rac1 via ROCK, while Rac1 inhibits RhoA through PAK. Our data suggest that in motile, polarized cells, RhoA–ROCK interactions prevail at the rear, whereas RhoA-DIA interactions dominate at the front where Rac1/Rho oscillations drive protrusions and retractions. At the rear, high RhoA and low Rac1 activities are maintained until a wave of oscillatory GTPase activities from the cell front reaches the rear, inducing transient GTPase oscillations and RhoA activity spikes. After the rear retracts, the initial GTPase pattern resumes. Our findings show how periodic, propagating GTPase waves coordinate distinct GTPase patterns at the leading and trailing edge dynamics in moving cells. eLife Sciences Publications, Ltd 2020-07-24 /pmc/articles/PMC7380942/ /pubmed/32705984 http://dx.doi.org/10.7554/eLife.58165 Text en © 2020, Bolado-Carrancio et al http://creativecommons.org/licenses/by/4.0/ http://creativecommons.org/licenses/by/4.0/This article is distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use and redistribution provided that the original author and source are credited. |
spellingShingle | Cell Biology Bolado-Carrancio, Alfonso Rukhlenko, Oleksii S Nikonova, Elena Tsyganov, Mikhail A Wheeler, Anne Garcia-Munoz, Amaya Kolch, Walter von Kriegsheim, Alex Kholodenko, Boris N Periodic propagating waves coordinate RhoGTPase network dynamics at the leading and trailing edges during cell migration |
title | Periodic propagating waves coordinate RhoGTPase network dynamics at the leading and trailing edges during cell migration |
title_full | Periodic propagating waves coordinate RhoGTPase network dynamics at the leading and trailing edges during cell migration |
title_fullStr | Periodic propagating waves coordinate RhoGTPase network dynamics at the leading and trailing edges during cell migration |
title_full_unstemmed | Periodic propagating waves coordinate RhoGTPase network dynamics at the leading and trailing edges during cell migration |
title_short | Periodic propagating waves coordinate RhoGTPase network dynamics at the leading and trailing edges during cell migration |
title_sort | periodic propagating waves coordinate rhogtpase network dynamics at the leading and trailing edges during cell migration |
topic | Cell Biology |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7380942/ https://www.ncbi.nlm.nih.gov/pubmed/32705984 http://dx.doi.org/10.7554/eLife.58165 |
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