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

Author:

Watabe TetsuyaORCID,Yamahira Shinya,Takakura Kanako,Thumkeo Dean,Narumiya Shuh,Matsuda MichiyukiORCID,Terai KentaORCID

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.

Publisher

Cold Spring Harbor Laboratory

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