YAP and TAZ regulate cell volume

被引:36
|
作者
Perez-Gonzalez, Nicolas A. [1 ]
Rochman, Nash D. [1 ]
Yao, Kai [2 ]
Tao, Jiaxiang [2 ]
Le, Minh-Tam Tran [1 ]
Flanaryi, Shannon [1 ]
Sablichi, Lucia [1 ]
Toler, Ben [1 ]
Crentsil, Eliana [1 ]
Takaesu, Felipe [1 ]
Lambrus, Bram [3 ]
Huang, Jessie [4 ]
Fu, Vivian [6 ,7 ]
Chengappa, Pragati [5 ]
Jones, Tia M. [5 ]
Holland, Andrew J. [3 ]
An, Steven [4 ]
Wirtz, Denis [1 ,8 ]
Petrie, Ryan J. [5 ]
Guan, Kun-Liang [6 ,7 ]
Sun, Sean X. [1 ,2 ,8 ]
机构
[1] Johns Hopkins Univ, Dept Chem & Biomol Engn, Baltimore, MD 21218 USA
[2] Johns Hopkins Univ, Dept Mech Engn, Baltimore, MD 21218 USA
[3] Johns Hopkins Univ, Sch Med, Dept Mol Biol & Genet, Baltimore, MD 21205 USA
[4] Johns Hopkins Bloomberg Sch Publ Hlth, Dept Environm Hlth & Engn, Baltimore, MD USA
[5] Drexel Univ, Dept Biol, Philadelphia, PA 19104 USA
[6] Univ Calif San Diego, Dept Pharmacol, La Jolla, CA 92093 USA
[7] Univ Calif San Diego, Moores Canc Ctr, La Jolla, CA 92093 USA
[8] Johns Hopkins Univ, Phys Sci Oncol Ctr, Baltimore, MD 21218 USA
来源
JOURNAL OF CELL BIOLOGY | 2019年 / 218卷 / 10期
基金
美国国家卫生研究院;
关键词
SIZE HOMEOSTASIS; HIPPO PATHWAY; GROWTH; INHIBITION; DYNAMICS; YAP/TAZ; MTOR;
D O I
10.1083/jcb.201902067
中图分类号
Q2 [细胞生物学];
学科分类号
071009 ; 090102 ;
摘要
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 PDZbinding 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 inhibitingmyosin 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.
引用
收藏
页码:3472 / 3488
页数:17
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