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YAP regulates cell mechanics by controlling focal adhesion assembly

Author

Listed:
  • Giorgia Nardone

    (International Clinical Research Center (ICRC), St Anne’s University Hospital)

  • Jorge Oliver-De La Cruz

    (International Clinical Research Center (ICRC), St Anne’s University Hospital)

  • Jan Vrbsky

    (International Clinical Research Center (ICRC), St Anne’s University Hospital)

  • Cecilia Martini

    (International Clinical Research Center (ICRC), St Anne’s University Hospital)

  • Jan Pribyl

    (CEITEC MU, Masaryk University)

  • Petr Skládal

    (CEITEC MU, Masaryk University)

  • Martin Pešl

    (International Clinical Research Center (ICRC), St Anne’s University Hospital
    Faculty of Medicine, Masaryk University)

  • Guido Caluori

    (International Clinical Research Center (ICRC), St Anne’s University Hospital)

  • Stefania Pagliari

    (International Clinical Research Center (ICRC), St Anne’s University Hospital)

  • Fabiana Martino

    (International Clinical Research Center (ICRC), St Anne’s University Hospital
    Faculty of Medicine, Masaryk University)

  • Zuzana Maceckova

    (Faculty of Medicine and Dentistry, Institute of Molecular and Translational Medicine, Palacky University Olomouc)

  • Marian Hajduch

    (Faculty of Medicine and Dentistry, Institute of Molecular and Translational Medicine, Palacky University Olomouc)

  • Andres Sanz-Garcia

    (Faculty of Pharmacy, University of Helsinki
    Institute of Advanced Biomedical Engineering and Science, Tokyo Women’s Medical University)

  • Nicola Maria Pugno

    (Laboratory of Bio-inspired and Graphene Nanomechanics, Environmental and Mechanical Engineering, University of Trento
    Ket-Lab, Italian Space Agency, Via del Politecnico snc
    School of Engineering and Materials Science, Queen Mary University of London)

  • Gorazd Bernard Stokin

    (International Clinical Research Center (ICRC), St Anne’s University Hospital)

  • Giancarlo Forte

    (International Clinical Research Center (ICRC), St Anne’s University Hospital
    Institute of Dentistry, University of Turku)

Abstract

Hippo effectors YAP/TAZ act as on–off mechanosensing switches by sensing modifications in extracellular matrix (ECM) composition and mechanics. The regulation of their activity has been described by a hierarchical model in which elements of Hippo pathway are under the control of focal adhesions (FAs). Here we unveil the molecular mechanism by which cell spreading and RhoA GTPase activity control FA formation through YAP to stabilize the anchorage of the actin cytoskeleton to the cell membrane. This mechanism requires YAP co-transcriptional function and involves the activation of genes encoding for integrins and FA docking proteins. Tuning YAP transcriptional activity leads to the modification of cell mechanics, force development and adhesion strength, and determines cell shape, migration and differentiation. These results provide new insights into the mechanism of YAP mechanosensing activity and qualify this Hippo effector as the key determinant of cell mechanics in response to ECM cues.

Suggested Citation

  • Giorgia Nardone & Jorge Oliver-De La Cruz & Jan Vrbsky & Cecilia Martini & Jan Pribyl & Petr Skládal & Martin Pešl & Guido Caluori & Stefania Pagliari & Fabiana Martino & Zuzana Maceckova & Marian Haj, 2017. "YAP regulates cell mechanics by controlling focal adhesion assembly," Nature Communications, Nature, vol. 8(1), pages 1-13, August.
    • Handle: RePEc:nat:natcom:v:8:y:2017:i:1:d:10.1038_ncomms15321
    DOI: 10.1038/ncomms15321
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    Cited by:

    1. Robin Caire & Estelle Audoux & Mireille Thomas & Elisa Dalix & Aurélien Peyron & Killian Rodriguez & Nicola Pordone & Johann Guillemot & Yann Dickerscheit & Hubert Marotte & François Vandenesch & Fréd, 2022. "YAP promotes cell-autonomous immune responses to tackle intracellular Staphylococcus aureus in vitro," Nature Communications, Nature, vol. 13(1), pages 1-19, December.
    2. Zhao Wang & Jan Lauko & Amanda W. Kijas & Elliot P. Gilbert & Petri Turunen & Ramanathan Yegappan & Dongxiu Zou & Jitendra Mata & Alan E. Rowan, 2023. "Snake venom-defined fibrin architecture dictates fibroblast survival and differentiation," Nature Communications, Nature, vol. 14(1), pages 1-16, December.
    3. Sara G. Romeo & Ilaria Secco & Edoardo Schneider & Christina M. Reumiller & Celio X. C. Santos & Anna Zoccarato & Vishal Musale & Aman Pooni & Xiaoke Yin & Konstantinos Theofilatos & Silvia Cellone Tr, 2023. "Human blood vessel organoids reveal a critical role for CTGF in maintaining microvascular integrity," Nature Communications, Nature, vol. 14(1), pages 1-18, December.
    4. Jiayu Liu & Chuanrong Zhao & Xue Xiao & Aohan Li & Yueqi Liu & Jianan Zhao & Linwei Fan & Zhenhui Liang & Wei Pang & Weijuan Yao & Wei Li & Jing Zhou, 2023. "Endothelial discoidin domain receptor 1 senses flow to modulate YAP activation," Nature Communications, Nature, vol. 14(1), pages 1-20, December.
    5. Alessandro Poli & Fabrizio A. Pennacchio & Andrea Ghisleni & Mariagrazia Gennaro & Margaux Lecacheur & Paulina Nastały & Michele Crestani & Francesca M. Pramotton & Fabio Iannelli & Galina Beznusenko , 2023. "PIP4K2B is mechanoresponsive and controls heterochromatin-driven nuclear softening through UHRF1," Nature Communications, Nature, vol. 14(1), pages 1-15, December.
    6. Ana Sousa-Ortega & Javier Vázquez-Marín & Estefanía Sanabria-Reinoso & Jorge Corbacho & Rocío Polvillo & Alejandro Campoy-López & Lorena Buono & Felix Loosli & María Almuedo-Castillo & Juan R. Martíne, 2023. "A Yap-dependent mechanoregulatory program sustains cell migration for embryo axis assembly," Nature Communications, Nature, vol. 14(1), pages 1-17, December.
    7. Zheng Zhang & Baoyong Sha & Lingzhu Zhao & Huan Zhang & Jinteng Feng & Cheng Zhang & Lin Sun & Meiqing Luo & Bin Gao & Hui Guo & Zheng Wang & Feng Xu & Tian Jian Lu & Guy M. Genin & Min Lin, 2022. "Programmable integrin and N-cadherin adhesive interactions modulate mechanosensing of mesenchymal stem cells by cofilin phosphorylation," Nature Communications, Nature, vol. 13(1), pages 1-14, December.

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