@article{32f12fa889a14430a46190619dacd97e,
title = "The Hippo pathway drives the cellular response to hydrostatic pressure",
abstract = "Cells need to rapidly and precisely react to multiple mechanical and chemical stimuli in order to ensure precise context-dependent responses. This requires dynamic cellular signalling events that ensure homeostasis and plasticity when needed. A less well-understood process is cellular response to elevated interstitial fluid pressure, where the cell senses and responds to changes in extracellular hydrostatic pressure. Here, using quantitative label-free digital holographic imaging, combined with genome editing, biochemical assays and confocal imaging, we analyse the temporal cellular response to hydrostatic pressure. Upon elevated cyclic hydrostatic pressure, the cell responds by rapid, dramatic and reversible changes in cellular volume. We show that YAP and TAZ, the co-transcriptional regulators of the Hippo signalling pathway, control cell volume and that cells without YAP and TAZ have lower plasma membrane tension. We present direct evidence that YAP/TAZ drive the cellular response to hydrostatic pressure, a process that is at least partly mediated via clathrin-dependent endocytosis. Additionally, upon elevated oscillating hydrostatic pressure, YAP/TAZ are activated and induce TEAD-mediated transcription and expression of cellular components involved in dynamic regulation of cell volume and extracellular matrix. This cellular response confers a feedback loop that allows the cell to robustly respond to changes in interstitial fluid pressure.",
keywords = "cell volume, endocytosis, holographic imaging, membrane tension, YAP/TAZ",
author = "Jiwon Park and Siyang Jia and Salter, {Donald M} and Bagnaninchi, {Pierre Olivier} and Hansen, {Carsten Gram}",
note = "Funding Information: Work ongoing in the Gram Hansen lab was supported by a University of Edinburgh Chancellor{\textquoteright}s Fellowship and start‐up fund, as well as now by Worldwide Cancer Research (19‐0238) and LifeArc‐CSO. This project was initiated by pump prime funding from the Bone Cancer Research Trust (BCRT), Sarcoma, UK (SUK202.2016), the Wellcome Trust‐University of Edinburgh Institutional Strategic Support Fund (ISSF3) and the Jonathan Haw Fund/ Kinross Trust. J.P. was funded by a MRC Precision Medicine DTP Studentship. S.J. by a scholarship from the Chinese Scholarship Council and the Edinburgh Global from University of Edinburgh. We furthermore acknowledge team members for helping with cell culturing and for insightful comments on this study. We acknowledge the technical support and guidance provided by the Centre for Reproductive Health SuRF Histology, Imaging and qPCR Facility staff as well as the QMRI Flow Cytometry and Cell Sorting Facility staff, and Dr Jessica Valli (ESRIC) at Heriot‐Watt University for FLIM expertise and imaging. Professor Kun‐Liang Guan (UCSD) and Assistant Professor Zhipeng Meng (University of Miami) are acknowledged for sharing gene‐edited HEK293A cell lines. For the purpose of open access, the author has applied a Creative Commons Attribution (CC BY) licence to any Author Accepted Manuscript version arising from this submission. Funding for Open Access was approved for this article. Funding Information: Work ongoing in the Gram Hansen lab was supported by a University of Edinburgh Chancellor{\textquoteright}s Fellowship and start-up fund, as well as now by Worldwide Cancer Research (19-0238) and LifeArc-CSO. This project was initiated by pump prime funding from the Bone Cancer Research Trust (BCRT), Sarcoma, UK (SUK202.2016), the Wellcome Trust-University of Edinburgh Institutional Strategic Support Fund (ISSF3) and the Jonathan Haw Fund/ Kinross Trust. J.P. was funded by a MRC Precision Medicine DTP Studentship. S.J. by a scholarship from the Chinese Scholarship Council and the Edinburgh Global from University of Edinburgh. We furthermore acknowledge team members for helping with cell culturing and for insightful comments on this study. We acknowledge the technical support and guidance provided by the Centre for Reproductive Health SuRF Histology, Imaging and qPCR Facility staff as well as the QMRI Flow Cytometry and Cell Sorting Facility staff, and Dr Jessica Valli (ESRIC) at Heriot-Watt University for FLIM expertise and imaging. Professor Kun-Liang Guan (UCSD) and Assistant Professor Zhipeng Meng (University of Miami) are acknowledged for sharing gene-edited HEK293A cell lines. For the purpose of open access, the author has applied a Creative Commons Attribution (CC BY) licence to any Author Accepted Manuscript version arising from this submission. Funding for Open Access was approved for this article. Publisher Copyright: {\textcopyright} 2022 The Authors. Published under the terms of the CC BY 4.0 license.",
year = "2022",
month = jul,
day = "4",
doi = "10.15252/embj.2021108719",
language = "English",
volume = "41",
pages = "e108719",
journal = "EMBO Journal",
issn = "0261-4189",
publisher = "Wiley-Blackwell",
number = "13",
}