دورية أكاديمية

Protein kinase C and calcineurin cooperatively mediate cell survival under compressive mechanical stress.

التفاصيل البيبلوغرافية
العنوان: Protein kinase C and calcineurin cooperatively mediate cell survival under compressive mechanical stress.
المؤلفون: van Drogen, Frank, Dechant, Reinhard, Peter, Matthias, Mishra, Ranjan, Sung Sik Lee, Soojung Oh, Noo Li Jeon
المصدر: Proceedings of the National Academy of Sciences of the United States of America; 12/19/2017, Vol. 114 Issue 51, p13471-13476, 6p
مصطلحات موضوعية: PROTEIN kinase C, STRAINS & stresses (Mechanics), CYTOSKELETON, MICROFLUIDICS, SINGLE cell proteins
مستخلص: 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 springlike 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. [ABSTRACT FROM AUTHOR]
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قاعدة البيانات: Complementary Index
الوصف
تدمد:00278424
DOI:10.1073/pnas.1709079114