Microtubules tune mechanosensitive cell responses

Shailaja Seetharaman (1, 2) , Benoit Vianay (3, 4, 5, 6, 7) , Vanessa Roca (1) , Aaron Farrugia (8) , Chiara de Pascalis (1) , Batiste Boëda (1) , Florent Dingli (9, 10) , Damarys Loew (9, 10) , Steṕhane Vassilopoulos (11) , Alexander Bershadsky (8) , Manuel Théry (3, 4, 12, 6, 7) , Sandrine Etienne-Manneville (1)

1 Polarité cellulaire, Migration et Cancer - Cell Polarity, Migration and Cancer
2 Université Paris Descartes, Sorbonne Paris Cité
3 IUH - Institut Universitaire d'Hématologie
4 INSERM - Institut National de la Santé et de la Recherche Médicale
5 CEA - Commissariat à l'énergie atomique et aux énergies alternatives
6 AP-HP - Hopital Saint-Louis [AP-HP]
7 UPCité - Université Paris Cité
8 NUS - National University of Singapore
9 Laboratoire de Spectrométrie de Masse Protéomique
10 PSL - Université Paris sciences et lettres
11 Centre de recherche en Myologie – U974 SU-INSERM
12 CEA - CEA- Saclay

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.

Domains: Subcellular Processes [q-bio.SC]

Shailaja Seetharaman, Benoit Vianay, Vanessa Roca, Aaron Farrugia, Chiara de Pascalis, et al.. Microtubules tune mechanosensitive cell responses. Nature Materials, 2021, ⟨10.1038/s41563-021-01108-x⟩. ⟨pasteur-03096554v2⟩