The Hippo pathway drives the cellular response to hydrostatic pressure

Jiwon Park, Siyang Jia, Donald M Salter, Pierre Olivier Bagnaninchi, Carsten Gram Hansen*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

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.

Original languageEnglish
Article numbere108719
Pages (from-to)e108719
JournalEMBO Journal
Volume41
Issue number13
Early online date15 Jun 2022
DOIs
Publication statusPublished - 4 Jul 2022

Keywords

  • cell volume
  • endocytosis
  • holographic imaging
  • membrane tension
  • YAP/TAZ

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