SCWISh network is essential for survival under mechanical pressure
| Autor: | Oskar Hallatschek, Jessica Choi, Morgan Delarue, Ori Hoxha, Gregory Poterewicz, Jona Kayser, Wonjung Yoo, Liam J. Holt |
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| Rok vydání: | 2017 |
| Předmět: |
0301 basic medicine
Saccharomyces cerevisiae Proteins Mechanotransduction Saccharomyces cerevisiae ved/biology.organism_classification_rank.species microfluidic Bioengineering Stress Mechanotransduction Cellular Cell wall 03 medical and health sciences Cell Wall MD Multidisciplinary Genetics 2.1 Biological and endogenous factors Aetiology Model organism Multidisciplinary biology MAP kinase kinase kinase Chemistry Kinase ved/biology compressive stress Cell Cycle Intracellular Signaling Peptides and Proteins Membrane Proteins Cell cycle Biological Sciences biology.organism_classification Actin cytoskeleton MAP Kinase Kinase Kinases Mechanical Cell biology Actin Cytoskeleton 030104 developmental biology Good Health and Well Being Mechanosensitive channels mechanosensing Stress Mechanical Cellular Biotechnology |
| Zdroj: | Proceedings of the National Academy of Sciences of the United States of America, vol 114, iss 51 |
| Popis: | Cells that proliferate within a confined environment build up mechanical compressive stress. For example, mechanical pressure emerges in the naturally space-limited tumor environment. However, little is known about how cells sense and respond to mechanical compression. We developed microfluidic bioreactors to enable the investigation of the effects of compressive stress on the growth of the genetically tractable model organism Saccharomyces cerevisiae We used this system to determine that compressive stress is partly sensed through a module consisting of the mucin Msb2 and the cell wall protein Sho1, which act together as a sensor module in one of the two major osmosensing pathways in budding yeast. This signal is transmitted via the MAPKKK kinase Ste11. Thus, we term this mechanosensitive pathway the "SMuSh" pathway, for Ste11 through Mucin/Sho1 pathway. The SMuSh pathway delays cells in the G1 phase of the cell cycle and improves cell survival in response to growth-induced pressure. We also found that the cell wall integrity (CWI) pathway contributes to the response to mechanical compressive stress. These latter results are confirmed in complimentary experiments in Mishra et al. [Mishra R, et al. (2017) Proc Natl Acad Sci USA, 10.1073/pnas.1709079114]. When both the SMuSh and the CWI pathways are deleted, cells fail to adapt to compressive stress, and all cells lyse at relatively low pressure when grown in confinement. Thus, we define a network that is essential for cell survival during growth under pressure. We term this mechanosensory system the SCWISh (survival through the CWI and SMuSh) network. |
| Databáze: | OpenAIRE |
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