1. YAP and TAZ regulate cell volume
- Author
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Ryan J. Petrie, Tia M. Jones, Jiaxiang Tao, Nicolas A. Perez-Gonzalez, Ben Toler, Shannon Flanary, Steven S. An, Pragati Chengappa, Minh Tam Tran Le, Kai Yao, Bram Lambrus, Nash D. Rochman, Jessie Huang, Andrew J. Holland, Felipe Takaesu, Lucia Sablich, Sean X. Sun, Kun-Liang Guan, Denis Wirtz, Vivian Fu, and Eliana Crentsil
- Subjects
Cell division ,Cells ,Cell ,Cell Cycle Proteins ,Biology ,Medical and Health Sciences ,Article ,03 medical and health sciences ,0302 clinical medicine ,medicine ,Humans ,Cytoskeleton ,Research Articles ,Cells, Cultured ,PI3K/AKT/mTOR pathway ,Cell Size ,030304 developmental biology ,0303 health sciences ,Cultured ,Cell Cycle ,HEK 293 cells ,Cell Biology ,Biological Sciences ,Cell cycle ,Cell biology ,HEK293 Cells ,medicine.anatomical_structure ,Cytoplasm ,Transcriptional Coactivator with PDZ-Binding Motif Proteins ,Trans-Activators ,030217 neurology & neurosurgery ,Intracellular ,Developmental Biology ,Transcription Factors - Abstract
Using a microfluidic method, it was found that YAP and TAZ are novel regulators of single-cell size and act independently of mTOR. YAP also influences cell cytoplasmic pressure and acts together with cytoskeletal tension to influence cell cycle progression., 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.
- Published
- 2019