Calcium transients trigger switch-like discharge of prostaglandin E2 in an extracellular signal-regulated kinase-dependent manner
Tetsuya Watabe,
Shinya Yamahira,
Kanako Takakura,
Dean Thumkeo,
Shuh Narumiya,
Michiyuki Matsuda,
Kenta Terai
Affiliations
Tetsuya Watabe
Research Center for Dynamic Living Systems, Graduate School of Biostudies, Kyoto University, Kyoto, Japan; Department of Pathology and Biology of Diseases, Graduate School of Medicine, Kyoto University, Kyoto, Japan
Shinya Yamahira
Research Center for Dynamic Living Systems, Graduate School of Biostudies, Kyoto University, Kyoto, Japan
Kanako Takakura
Research Center for Dynamic Living Systems, Graduate School of Biostudies, Kyoto University, Kyoto, Japan
Dean Thumkeo
Department of Drug Discovery Medicine, Graduate School of Medicine, Kyoto University, Kyoto, Japan
Shuh Narumiya
Department of Drug Discovery Medicine, Graduate School of Medicine, Kyoto University, Kyoto, Japan
Research Center for Dynamic Living Systems, Graduate School of Biostudies, Kyoto University, Kyoto, Japan; Department of Pathology and Biology of Diseases, Graduate School of Medicine, Kyoto University, Kyoto, Japan; Institute for Integrated Cell-Material Sciences, Kyoto University, Kyoto, Japan
Prostaglandin E2 (PGE2) is a key player in a plethora of physiological and pathological events. Nevertheless, little is known about the dynamics of PGE2 secretion from a single cell and its effect on the neighboring cells. Here, by observing confluent Madin–Darby canine kidney (MDCK) epithelial cells expressing fluorescent biosensors, we demonstrate that calcium transients in a single cell cause PGE2-mediated radial spread of PKA activation (RSPA) in neighboring cells. By in vivo imaging, RSPA was also observed in the basal layer of the mouse epidermis. Experiments with an optogenetic tool revealed a switch-like PGE2 discharge in response to the increasing cytoplasmic Ca2+ concentrations. The cell density of MDCK cells correlated with the frequencies of calcium transients and the following RSPA. The extracellular signal-regulated kinase (ERK) activation also enhanced the frequency of RSPA in MDCK and in vivo. Thus, the PGE2 discharge is regulated temporally by calcium transients and ERK activity.
