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

The G 1 -S transition is promoted by Rb degradation via the E3 ligase UBR5 DOI Creative Commons
Shuyuan Zhang, Lucas Fuentes Valenzuela, Evgeny Zatulovskiy

et al.

Science Advances, Journal Year: 2024, Volume and Issue: 10(43)

Published: Oct. 23, 2024

Mammalian cells make the decision to divide at G 1 -S transition in response diverse signals impinging on retinoblastoma protein Rb, a cell cycle inhibitor and tumor suppressor. Passage through is initially driven by Rb inactivation via phosphorylation Rb’s decreasing concentration . While many studies have identified mechanisms of phosphorylation, mechanism underlying was unknown. Here, we found that decrease requires E3 ubiquitin ligase UBR5. UBR5 knockout increased early , exhibited lower rate, are more sensitive inhibition cyclin-dependent kinase 4/6 (Cdk4/6). This last observation suggests can strengthen efficacy Cdk4/6 inhibitor–based cancer therapies.

Language: Английский

Citations

1
Mechanochemical control systems regulating animal cell size DOI
Heather E. Rizzo, Andy L Zhang, Margaret L. Gardel

et al.

Current Opinion in Cell Biology, Journal Year: 2024, Volume and Issue: 91, P. 102443 - 102443

Published: Nov. 6, 2024

Language: Английский

Citations

1
Cytoskeletal activation of NHE1 regulates mechanosensitive cell volume adaptation and proliferation DOI Creative Commons
Qin Ni,

Zhuoxu Ge,

Yizeng Li

et al.

Cell Reports, Journal Year: 2024, Volume and Issue: 43(12), P. 114992 - 114992

Published: Nov. 22, 2024

Language: Английский

Citations

1
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: Dec. 23, 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

1
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

Citations

3