YAP and TAZ regulate cell volume

Abstract

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.

PGC1/PPAR Drive Cardiomyocyte Maturation through Regulation of Yap1 and SF3B2

“…We also found that PGC1/PPAR directly regulates Yap1, a conserved transcriptional regulator of organ/cell size (Lloyd, 2013). The role of Yap1 has been extensively studied on CM proliferation for heart repair (Wang et al, 2018), but growing evidence suggests its critical role in cellular hypertrophy (Perez-Gonzalez et al, 2019;Windmueller and Morrisey, 2015). Similarly, our data showed that Yap1 is a key mediator of PGC1/PPAR for CM growth.…”

“…Calcium handling genes and ion channels including Ryr2, Atp2a2, Casq1, critical for contractility development, were continually upregulated while genes involved in cell cycle, including Cdk1, Cdk4, Ccnd1 (Mohamed et al, 2018;Yang et al, 2014), were downregulated ( Figure 1F). Conserved genes governing cellular hypertrophy, including Mtor, Yap1, Igf1r (Lloyd, 2013;Perez-Gonzalez et al, 2019), were modestly downregulated or maintained in expression as they are known to regulate cell volume ( Figure 1F). Gene ontology (GO) analysis indicated that genes related to muscle contraction and cellular metabolism are highly regulated during the process ( Figure S1A).…”

CTRL – a label-free artificial intelligence method for dynamic measurement of single-cell volume

“…Exclusion method (FXm), first proposed in 1983 14 and subsequently developed and refined by several groups [18][19][20] . Cells are seeded in a micro-fabricated chamber and a membrane-impermeable high molecular weight fluorescent dye (e.g.…”

CTRL: a label-free method for dynamic measurement of single-cell volume

“…An accurate and high throughput method of cell volume quantification is the Fluorescence Exclusion method (FXm), first proposed in 1983 14 and subsequently developed and refined by several groups [18][19][20] . Cells are seeded in a micro-fabricated chamber and a membrane-impermeable high molecular weight fluorescent dye (e.g.…”

“…Cell suspension alters the cell shape and biochemical signaling from the extracellular matrix, and also potentially affecting cell size. None of these methods has been successfully applied to measure mammalian cell growth at the single-cell level.While sensitive and accurate methods have been developed to measure single-cell mass over time 17 , the relationship between cell size and mass is not always clear.An accurate and high throughput method of cell volume quantification is the Fluorescence Exclusion method (FXm), first proposed in 1983 14 and subsequently developed and refined by several groups [18][19][20] . Cells are seeded in a micro-fabricated chamber and a membrane-impermeable high molecular weight fluorescent dye (e.g.…”