Homer2 regulates amylase secretion via physiological calcium oscillations in mouse parotid gland acinar cells

Abstract

The salivary glands secrete saliva, which plays a role in the maintenance of a healthy oral environment. Under physiological conditions, saliva secretion within the acinar cells of the gland is regulated by stimulation of specific calcium (Ca 2+ ) signaling mechanisms such as increases in the intracellular Ca 2+ concentration ([Ca 2+ ] i ) via store-operated Ca 2+ entry, which involves components such as Orai1, transient receptor potential (TRP) canonical 1, stromal interaction molecules, and inositol 1,4,5-triphosphate (IP 3 ) receptors (IP 3 Rs). Homer proteins are scaffold proteins that bind to G protein-coupled receptors, IP 3 Rs, ryanodine receptors, and TRP channels. However, their exact role in Ca 2+ signaling in the salivary glands remains unknown. In the present study, we investigated the role of Homer2 in Ca 2+ signaling and saliva secretion in parotid gland acinar cells under physiological conditions. Deletion of Homer2 (Homer2 −/− ) markedly decreased the amplitude of [Ca 2+ ] i oscillations via the stimulation of carbachol, which is physiologically concentrated in parotid acinar cells, whereas the frequency of [Ca 2+ ] i oscillations showed no difference between wild-type and Homer2 −/− mice. Homer2 −/− mice also showed a significant decrease in amylase release by carbachol in the parotid gland in a dose-dependent manner. These results suggest that Homer2 plays a critical role in maintaining [Ca 2+ ] i concentration and secretion of saliva in mouse parotid gland acinar cells.