YAP and TAZ regulate cell volume

Nicolas A Perez-Gonzalez; Nash D Rochman; Kai Yao; Jiaxiang Tao; Minh-Tam Tran Le; Shannon Flanary; Lucia Sablich; Ben Toler; Eliana Crentsil; Felipe Takaesu; Bram Lambrus; Jessie Huang; Vivian Fu; Pragati Chengappa; Tia M Jones; Andrew J Holland; Steven An; Denis Wirtz; Ryan J Petrie; Kun-Liang Guan; Sean X Sun

doi:10.1083/JCB.201902067

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YAP and TAZ regulate cell volume

Nicolas A Perez-Gonzalez, Nash D Rochman, Kai Yao, Jiaxiang Tao, Minh-Tam Tran Le, Shannon Flanary, Lucia Sablich, Ben Toler, Eliana Crentsil, Felipe Takaesu, …

The Journal of cell biology, Vol.218(10), pp.3472-3488

10/07/2019

DOI: https://doi.org/10.1083/JCB.201902067

PMCID: PMC6781432

PMID: 31481532

Abstract

Transcription Factors - metabolism

Cell Cycle

Humans

Cell Cycle Proteins - metabolism

Cells, Cultured

HEK293 Cells

Cytoskeleton - metabolism

Cell Size

Trans-Activators - metabolism

How mammalian cells regulate their physical size is currently poorly understood, in part due to the difficulty in accurately quantifying cell volume in a high-throughput manner. Here, using the fluorescence exclusion method, we demonstrate that the mechanosensitive transcriptional regulators YAP (Yes-associated protein) and TAZ (transcriptional coactivator with PDZ-binding motif) are regulators of single-cell volume. The role of YAP/TAZ in volume regulation must go beyond its influence on total cell cycle duration or cell shape to explain the observed changes in volume. Moreover, for our experimental conditions, volume regulation by YAP/TAZ is independent of mTOR. Instead, we find that YAP/TAZ directly impacts the cell division volume, and YAP is involved in regulating intracellular cytoplasmic pressure. Based on the idea that YAP/TAZ is a mechanosensor, we find that inhibiting myosin assembly and cell tension slows cell cycle progression from G1 to S. These results suggest that YAP/TAZ may be modulating cell volume in combination with cytoskeletal tension during cell cycle progression.

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Title: YAP and TAZ regulate cell volume
Creators: Nicolas A Perez-Gonzalez - Department of Chemical and Biomolecular Engineering, Johns Hopkins University, Baltimore, MD
Nash D Rochman - Department of Chemical and Biomolecular Engineering, Johns Hopkins University, Baltimore, MD
Kai Yao - Department of Mechanical Engineering, Johns Hopkins University, Baltimore, MD
Jiaxiang Tao - Department of Mechanical Engineering, Johns Hopkins University, Baltimore, MD
Minh-Tam Tran Le - Department of Chemical and Biomolecular Engineering, Johns Hopkins University, Baltimore, MD
Shannon Flanary - Department of Chemical and Biomolecular Engineering, Johns Hopkins University, Baltimore, MD
Lucia Sablich - Department of Chemical and Biomolecular Engineering, Johns Hopkins University, Baltimore, MD
Ben Toler - Department of Chemical and Biomolecular Engineering, Johns Hopkins University, Baltimore, MD
Eliana Crentsil - Department of Chemical and Biomolecular Engineering, Johns Hopkins University, Baltimore, MD
Felipe Takaesu - Department of Chemical and Biomolecular Engineering, Johns Hopkins University, Baltimore, MD
Bram Lambrus - Department of Molecular Biology and Genetics, Johns Hopkins University, School of Medicine, Baltimore, MD
Jessie Huang - Department of Environmental Health and Engineering, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD
Vivian Fu - Department of Pharmacology and Moores Cancer Center, University of California, San Diego, La Jolla, CA
Pragati Chengappa - Department of Biology, Drexel University, Philadelphia, PA
Tia M Jones - Department of Biology, Drexel University, Philadelphia, PA
Andrew J Holland - Department of Molecular Biology and Genetics, Johns Hopkins University, School of Medicine, Baltimore, MD
Steven An - Department of Environmental Health and Engineering, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD
Denis Wirtz - Physical Sciences in Oncology Center, Johns Hopkins University, Baltimore, MD
Ryan J Petrie - Department of Biology, Drexel University, Philadelphia, PA
Kun-Liang Guan - Department of Pharmacology and Moores Cancer Center, University of California, San Diego, La Jolla, CA
Sean X Sun - Physical Sciences in Oncology Center, Johns Hopkins University, Baltimore, MD
Publication Details: The Journal of cell biology, Vol.218(10), pp.3472-3488
Date published: 10/07/2019
Grant note: R01 GM101464 / NIGMS NIH HHS R01 GM114119 / NIGMS NIH HHS
Academic Unit: Clinical and Translational Research
Language: English
Resource Type: Journal article
Identifiers: 991031654821504646