Regulation of the expression and function of TRPCs and Orai1 by Homer2 in mouse pancreatic acinar cells

Abstract

Under physiological conditions, calcium (Ca 2+ ) regulates essential functions of polarized secretory cells by the stimulation of specific Ca 2+ signaling mechanisms, such as increases in intracellular Ca 2+ concentration ([Ca 2+ ] i ) via the store-operated Ca 2+ entry (SOCE) and the receptor-operated Ca 2+ entry (ROCE). Homer proteins are scaffold proteins that interact with G protein-coupled receptors, inositol 1,4,5-triphosphate (IP 3 ) receptors, Orai1-stromal interaction molecule 1, and transient receptor potential canonical (TRPC) channels. However, their role in the Ca 2+ signaling in exocrine cells remains unknown. In this study, we investigated the role of Homer2 in the Ca 2+ signaling and regulatory channels to mediate SOCE and ROCE in pancreatic acinar cells. Deletion of Homer2 (Homer2 –/– ) markedly increased the expression of TRPC3, TRPC6, and Orai1 in pancreatic acinar cells, whereas these expressions showed no difference in whole brains of wild-type and Homer2 –/– mice. Furthermore, the response of Ca 2+ entry by carbachol also showed significant changes to the patterns regulated by specific blockers of SOCE and ROCE in pancreatic acinar cells of Homer2 –/– mice. Thus, these results suggest that Homer2 plays a critical role in the regulatory action of the [Ca 2+ ] i via SOCE and ROCE in mouse pancreatic acinar cells.