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Microtubules tune mechanosensitive cell responses

View ORCID ProfileShailaja Seetharaman, Benoit Vianay, Vanessa Roca, Chiara De Pascalis, Batiste Boëda, Florent Dingli, Damarys Loew, Stéphane Vassilopoulos, Manuel Théry, Sandrine Etienne-Manneville
doi: https://doi.org/10.1101/2020.07.22.205203
Shailaja Seetharaman
1Cell Polarity, Migration and Cancer Unit, Institut Pasteur, UMR3691 CNRS, Equipe Labellisée Ligue Contre le Cancer, F-75015, Paris, France
2Université Paris Descartes, Sorbonne Paris Cité, 12 Rue de l’École de Médecine, 75006 Paris, France
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  • ORCID record for Shailaja Seetharaman
Benoit Vianay
3Paris University, INSERM, CEA, Hôpital Saint Louis, Institut Universitaire d’Hematologie, Paris, France
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Vanessa Roca
1Cell Polarity, Migration and Cancer Unit, Institut Pasteur, UMR3691 CNRS, Equipe Labellisée Ligue Contre le Cancer, F-75015, Paris, France
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Chiara De Pascalis
1Cell Polarity, Migration and Cancer Unit, Institut Pasteur, UMR3691 CNRS, Equipe Labellisée Ligue Contre le Cancer, F-75015, Paris, France
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Batiste Boëda
1Cell Polarity, Migration and Cancer Unit, Institut Pasteur, UMR3691 CNRS, Equipe Labellisée Ligue Contre le Cancer, F-75015, Paris, France
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Florent Dingli
4Institut Curie, PSL Research University, Centre de Recherche, Laboratoire de Spectrométrie de Masse Protéomique, 26 rue d’Ulm, Paris 75248 Cedex 05, France
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Damarys Loew
4Institut Curie, PSL Research University, Centre de Recherche, Laboratoire de Spectrométrie de Masse Protéomique, 26 rue d’Ulm, Paris 75248 Cedex 05, France
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Stéphane Vassilopoulos
5Sorbonne Université, INSERM UMRS 974, Institute of Myology, Paris, France
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Manuel Théry
3Paris University, INSERM, CEA, Hôpital Saint Louis, Institut Universitaire d’Hematologie, Paris, France
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Sandrine Etienne-Manneville
1Cell Polarity, Migration and Cancer Unit, Institut Pasteur, UMR3691 CNRS, Equipe Labellisée Ligue Contre le Cancer, F-75015, Paris, France
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  • For correspondence: setienne@pasteur.fr
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Abstract

Mechanotransduction is a process by which cells sense the mechanical properties of their surrounding environment and adapt accordingly to perform cellular functions such as adhesion, migration and differentiation. Integrin-mediated focal adhesions are major sites of mechanotransduction and their connection with the actomyosin network is crucial for mechanosensing as well as the generation and transmission of forces onto the substrate. Despite having emerged as major regulators of cell adhesion and migration, the contribution of microtubules to mechanotransduction still remains elusive. Here, we show that actomyosin-dependent mechanosensing of substrate rigidity controls microtubule acetylation, a tubulin post-translational modification, by promoting the recruitment of the alpha-tubulin acetyl transferase (αTAT1) to focal adhesions. Microtubule acetylation, in turn, promotes GEF-H1 mediated RhoA activation, actomyosin contractility and traction forces. Our results reveal a fundamental crosstalk between microtubules and actin in mechanotransduction, which contributes to mechanosensitive cell adhesion and migration.

Competing Interest Statement

The authors have declared no competing interest.

Copyright 
The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under a CC-BY-NC-ND 4.0 International license.
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Posted July 23, 2020.
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Microtubules tune mechanosensitive cell responses
Shailaja Seetharaman, Benoit Vianay, Vanessa Roca, Chiara De Pascalis, Batiste Boëda, Florent Dingli, Damarys Loew, Stéphane Vassilopoulos, Manuel Théry, Sandrine Etienne-Manneville
bioRxiv 2020.07.22.205203; doi: https://doi.org/10.1101/2020.07.22.205203
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Microtubules tune mechanosensitive cell responses
Shailaja Seetharaman, Benoit Vianay, Vanessa Roca, Chiara De Pascalis, Batiste Boëda, Florent Dingli, Damarys Loew, Stéphane Vassilopoulos, Manuel Théry, Sandrine Etienne-Manneville
bioRxiv 2020.07.22.205203; doi: https://doi.org/10.1101/2020.07.22.205203

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