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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...

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Autores principales: Bolado-Carrancio, Alfonso, Rukhlenko, Oleksii S, Nikonova, Elena, Tsyganov, Mikhail A, Wheeler, Anne, Garcia-Munoz, Amaya, Kolch, Walter, von Kriegsheim, Alex, Kholodenko, Boris N
Formato: Online Artículo Texto
Lenguaje:English
Publicado: eLife Sciences Publications, Ltd 2020
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.
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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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