Cytoskeletal activation of NHE1 regulates mechanosensitive cell volume adaptation and proliferation DOI Open Access
Qin Ni,

Zhuoxu Ge,

Yizeng Li

et al.

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2023, Volume and Issue: unknown

Published: Sept. 3, 2023

Mammalian cells can rapidly respond to osmotic and hydrostatic pressure imbalances during an environmental change, generating large fluxes of water ions that alter cell volume within minutes. While the role ion pump leak in regulation has been well-established, potential contribution actomyosin cytoskeleton its interplay with transporters is unclear. We discovered a system controlled by cytoskeletal activation transporters. After hypotonic shock, normal-like (NIH-3T3, MCF-10A, others) display slow secondary increase (SVI) following immediate regulatory decrease. show SVI initiated stress induced Ca 2+ influx through stretch activated channel Piezo1, which subsequently triggers remodeling. The network further activates NHE1 their synergistic linker ezrin, inducing after initial recovery. find absent cancer lines such as HT1080 MDA-MB-231, where dominated intrinsic response A similar also be achieved mechanical stretching. On compliant substrates contractility attenuated, generation abolished. Moreover, nuclear deformation, leading significant, transcriptomic change 3T3 cells, phenomenon again cells. shock hinders ERK-dependent growth, deficient are unresponsive inhibitory effects. Overall, our findings reveal critical actomyosin-mediated mechanosensation transport, volume, transcriptomics, proliferation.

Language: Английский

Increasing cell size remodels the proteome and promotes senescence DOI Creative Commons
Michael C. Lanz, Evgeny Zatulovskiy, Matthew P. Swaffer

et al.

Molecular Cell, Journal Year: 2022, Volume and Issue: 82(17), P. 3255 - 3269.e8

Published: Aug. 19, 2022

Language: Английский

Citations

144
Genome dilution by cell growth drives starvation-like proteome remodeling in mammalian and yeast cells DOI
Michael C. Lanz, Shuyuan Zhang, Matthew P. Swaffer

et al.

Nature Structural & Molecular Biology, Journal Year: 2024, Volume and Issue: unknown

Published: July 24, 2024

Language: Английский

Citations

9
Single-cell monitoring of dry mass and dry mass density reveals exocytosis of cellular dry contents in mitosis DOI Creative Commons
Teemu P. Miettinen, Kevin S Ly, Alice Lam

et al.

eLife, Journal Year: 2022, Volume and Issue: 11

Published: May 10, 2022

Cell mass and composition change with cell cycle progression. Our previous work characterized buoyant dynamics in mitosis (Miettinen et al., 2019), but how dry has remained unclear. To better understand mitotic growth compositional changes, we develop a single-cell approach for monitoring the density of that every ~75 s 1.3% 0.3% measurement precision, respectively. We find suspension grown mammalian cells lose increase following entry. These changes display large, non-genetic cell-to-cell variability, are reversed at metaphase-anaphase transition, after which continues accumulating. The causes to differ specifically early mitosis, thus reconciling existing literature on growth. Mechanistically, lysosomal exocytosis, inhibition exocytosis decreases loss mitosis. Overall, our provides new density, reveals is coupled extensive exocytosis-mediated secretion cellular contents.

Language: Английский

Citations

34
Delineation of proteome changes driven by cell size and growth rate DOI Creative Commons
Evgeny Zatulovskiy, Michael C. Lanz, Shuyuan Zhang

et al.

Frontiers in Cell and Developmental Biology, Journal Year: 2022, Volume and Issue: 10

Published: Sept. 5, 2022

Increasing cell size drives changes to the proteome, which affects physiology. As increases, some proteins become more concentrated while others are diluted. a result, state of continuously with increasing size. In addition these proteomic changes, large cells have lower growth rate (protein synthesis per unit volume). That both cell's proteome and change suggests they may be interdependent. To test this, we used quantitative mass spectrometry measure how in response mTOR inhibitor rapamycin, decreases cellular has only minimal effect on We found that inhibition, cell, remodel similar ways. This many effects mediated by size-dependent slowdown rate. For example, previously reported expression senescence markers could reflect declining rather than its

Language: Английский

Citations

23
Cell Size Contributes to Single-Cell Proteome Variation DOI
Michael C. Lanz, Lucas Fuentes Valenzuela, Joshua E. Elias

et al.

Journal of Proteome Research, Journal Year: 2023, Volume and Issue: 22(12), P. 3773 - 3779

Published: Nov. 1, 2023

Accurate measurements of the molecular composition single cells will be necessary for understanding relationship between gene expression and function in diverse cell types. One most important phenotypes that differs is their size, which was recently shown to an determinant proteome populations similarly sized cells. We, therefore, sought test if effects size on protein concentrations were also evident single-cell proteomics data. Using relative a set reference proteins estimate cell's DNA-to-cell volume ratio, we found differences explain significant amount cell-to-cell variance two published data sets.

Language: Английский

Citations

16
The G1/S transition in mammalian stem cellsin vivois autonomously regulated by cell size DOI Open Access
Shicong Xie, Shuyuan Zhang, Gustavo de Medeiros

et al.

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2024, Volume and Issue: unknown

Published: April 11, 2024

Cell growth and division must be coordinated to maintain a stable cell size, but how this coordination is implemented in multicellular tissues remains unclear. In unicellular eukaryotes, autonomous size control mechanisms couple with little extracellular input. However, we do not know if operate the same way or whether cycle progression are separately controlled by cell-extrinsic signals. Here, address question tracking single epidermal stem cells growing adult mice. We find that cell-autonomous mechanism, dependent on RB pathway, sets timing of S phase entry based cell's current size. Cell-extrinsic variations cellular microenvironment affect rates coupling. Our work reassesses long-standing models regulation within complex metazoan identifies as critical mechanism regulating divisions

Language: Английский

Citations

4
Genome concentration limits cell growth and modulates proteome composition in Escherichia coli DOI Creative Commons
Jarno Mäkelä, Alexandros Papagiannakis, Wei-Hsiang Lin

et al.

eLife, Journal Year: 2024, Volume and Issue: 13

Published: May 10, 2024

Defining the cellular factors that drive growth rate and proteome composition is essential for understanding manipulating systems. In bacteria, ribosome concentration known to be a constraining factor of cell rate, while gene usually assumed not limiting. Here, using single-molecule tracking, quantitative single-cell microscopy, modeling, we show genome dilution in Escherichia coli cells arrested DNA replication limits total RNA polymerase activity within physiological sizes across tested nutrient conditions. This rapid-onset limitation on bulk transcription results sub-linear scaling active ribosomes with size sub-exponential growth. Such downstream effects translation are near-immediately detectable nutrient-rich medium, but delayed nutrient-poor conditions, presumably due buffering activities. sequencing tandem-mass-tag mass spectrometry experiments further reveal remodels relative abundance mRNAs proteins at global level. Altogether, our findings indicate chromosome limiting modulator transcriptome E. . Experiments Caulobacter crescentus comparison eukaryotic studies identify broadly conserved concentration-dependent principles expression.

Language: Английский

Citations

4
What programs the size of animal cells? DOI Creative Commons
Shixuan Liu, Ceryl Tan, Mike Tyers

et al.

Frontiers in Cell and Developmental Biology, Journal Year: 2022, Volume and Issue: 10

Published: Nov. 1, 2022

The human body is programmed with definite quantities, magnitudes, and proportions. At the microscopic level, such sizes manifest in individual cells - different cell types are characterized by distinct whereas of same type highly uniform size. How do a population maintain uniformity size, how changes target size programmed? A convergence recent historical studies suggest just as thermostat maintains room temperature proliferating animal similarly maintained homeostatic mechanisms. In this review, we first summarize old new literature on existence checkpoints, then discuss additional advances study homeostasis that involve feedback regulation cellular growth rate. We further progress molecules underlie checkpoints mechanisms specify setpoints. Lastly, less-well explored teleological question: why does matter what functional importance control?

Language: Английский

Citations

17
The environmental stress response regulates ribosome content in cell cycle-arrested S. cerevisiae DOI Creative Commons

Allegra Terhorst,

Arzu Sandikci,

Charles A. Whittaker

et al.

Frontiers in Cell and Developmental Biology, Journal Year: 2023, Volume and Issue: 11

Published: April 12, 2023

Prolonged cell cycle arrests occur naturally in differentiated cells and response to various stresses such as nutrient deprivation or treatment with chemotherapeutic agents. Whether how survive prolonged is not clear. Here, we used

Language: Английский

Citations

10
Impact of G1 phase kinetics on the acquisition of stemness in cancer cells: the critical role of cyclin D DOI
Yasin Ahmadi,

Tahran Faiq,

Sakhavat Abolhasani

et al.

Molecular Biology Reports, Journal Year: 2025, Volume and Issue: 52(1)

Published: Feb. 14, 2025

Language: Английский

Citations

0