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RISS 인기검색어
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- 저자 : van Drogen, Frank (검색결과 1 건)
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Mishra, Ranjan,van Drogen, Frank,Dechant, Reinhard,Oh, Soojung,Jeon, Noo Li,Lee, Sung Sik,Peter, Matthias National Academy of Sciences 2017 PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF Vol.114 No.51
<P><B>Significance</B></P><P>Cells are constantly exposed to a variety of mechanical cues, and respond by activating conserved signaling pathways that modulate their profiliation and intracellular organization. For instance, cells in solid tumors experience sustained compression from the microenvironment, and compressive stress is known to trigger an invasive phenotype in some cancer cells. However, despite its importance for health and disease, the specific mechanosensors and the downstream signaling network mediating these physiological responses remain largely unknown, in part due to the lack of appropriate experimental systems. Here, we develop a microfluidic platform that allows triggering compressive mechanical stress in a reversible and controllable manner, and we identify cell surface receptors that specifically sense compressive mechanical stress and generate synergistic cellular responses.</P><P>Cells experience compressive stress while growing in limited space or migrating through narrow constrictions. To survive such stress, cells reprogram their intracellular organization to acquire appropriate mechanical properties. However, the mechanosensors and downstream signaling networks mediating these changes remain largely unknown. Here, we have established a microfluidic platform to specifically trigger compressive stress, and to quantitatively monitor single-cell responses of budding yeast in situ. We found that yeast senses compressive stress via the cell surface protein Mid2 and the calcium channel proteins Mid1 and Cch1, which then activate the Pkc1/Mpk1 MAP kinase pathway and calcium signaling, respectively. Genetic analysis revealed that these pathways work in parallel to mediate cell survival. Mid2 contains a short intracellular tail and a serine−threonine-rich extracellular domain with spring-like properties, and both domains are required for mechanosignaling. Mid2-dependent spatial activation of the Pkc1/Mpk1 pathway depolarizes the actin cytoskeleton in budding or shmooing cells, thereby antagonizing polarized growth to protect cells under compressive stress conditions. Together, these results identify a conserved signaling network responding to compressive mechanical stress, which, in higher eukaryotes, may ensure cell survival in confined environments.</P>
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