Calcium transients trigger switch-like discharge of prostaglandin E2in an extracellular signal-regulated kinase-dependent manner

Abstract

AbstractProstaglandin E2(PGE2) is a key player in a plethora of physiological and pathological events. Nevertheless, little is known about the dynamics of PGE2secretion 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. Byin vivoimaging, RSPA was also observed in the basal layer of the mouse epidermis. Experiments with an optogenetic tool revealed a switch-like PGE2discharge 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 andin vivo. Thus, the PGE2discharge is regulated temporally by calcium transients and ERK activity.