Regulation of the expression and function of TRPCs and Orai1 by Homer2 in mouse pancreatic acinar cells
강정윤, 강남주, 양유미,
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강정윤 ( Kang Jung-Yun ) - Yonsei University College of Dentistry Department of Oral Biology
강남주 ( Kang Nam-Ju ) - Yonsei University College of Dentistry Department of Oral Biology
양유미 ( Yang Yu-Mi ) - Yonsei University College of Dentistry Department of Oral Biology
Abstract
Under physiological conditions, calcium (Ca2+) regulates essential functions of polarized secretory cells by the stimulation of specific Ca2+ signaling mechanisms, such as increases in intracellular Ca2+ concentration ([Ca2+]i) via the store-operated Ca2+ entry (SOCE) and the receptor-operated Ca2+ entry (ROCE). Homer proteins are scaffold proteins that interact with G protein-coupled receptors, inositol 1,4,5-triphosphate (IP3) receptors, Orai1-stromal interaction molecule 1, and transient receptor potential canonical (TRPC) channels. However, their role in the Ca2+ signaling in exocrine cells remains unknown. In this study, we investigated the role of Homer2 in the Ca2+ 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 Ca2+ 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 [Ca2+]i via SOCE and ROCE in mouse pancreatic acinar cells.
키워드
Calcium signaling; Acinar cells; Homer scaffolding proteins; Physiological phenomena
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