Details

Autor(en) / Beteiligte

• Mishra, Ranjan
• van Drogen, Frank
• Dechant, Reinhard
• Oh, Soojung
• Jeon, Noo Li
• Lee, Sung Sik
• Peter, Matthias

Titel

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

Ist Teil von

• Proceedings of the National Academy of Sciences - PNAS, 2017-12, Vol.114 (51), p.13471-13476

Ort / Verlag

United States: National Academy of Sciences

Erscheinungsjahr

2017

Link zum Volltext

Quelle

EZB Electronic Journals Library

Beschreibungen/Notizen

• 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.