CRAC channel regulation of innate immune cells in health and disease. (March 2019)

• Record Type: Journal Article
• Authors: Clemens, Regina A.; Lowell, Clifford A.
• Is Part Of: Cell calcium. Volume 78(2019)
• Page Start: 56
• Page End: 65
• Publication Date: 2019-03
• Subjects: Calcium -- Store-operated calcium entry -- CRAC channel -- ORAI -- STIM -- Neutrophil -- Mast cell -- Monocyte -- Dendritic cell -- Inflammation -- Orai1 -- Orai2 -- Orai3 -- Stim1 -- Stim2; Calcium -- Metabolism -- Periodicals; Vertebrates -- Physiology -- Periodicals; Calcium -- Physiological effect -- Periodicals; Cell physiology -- Periodicals; Calcium in the body -- Periodicals; 572.516
• DOI: 10.1016/j.ceca.2019.01.003
• Languages: English
• ISSNs: 0143-4160

Abstract

Graphical abstract: Highlights: ORAI-family channels play a dominant role in store-operated calcium signaling in innate immune cells. CRAC channels are required for IgE-mediated mast cell activation. Store-operated calcium entry is required for many neutrophil functions; the contribution of ORAI family members remains under investigation. Store-operated calcium signaling is required for proper antigen processing in dendritic cells. Store-operated calcium entry has diverse effects in innate immune cells, with implications for host defense, allergy and inflammatory disease. Abstract: Calcium is a major intracellular signaling messenger in innate immune cells. Similar to other immune cell subsets, the majority of calcium entry into innate immune cells is induced by cell surface receptors that stimulate store-operated calcium entry through calcium-release activated calcium (CRAC) channels. Since the molecular description of the STIM family of calcium sensors and the ORAI family of CRAC channel proteins, the majority of studies support a dominant role for these proteins in calcium signaling in innate cells. In reviewing the literature on CRAC channel function in innate cells, several general themes emerge. All innate cells express multiple members of the STIM and ORAI family members, however the ratio and relative contribution of individual isoforms changes depending on the cell type and activation state of the cell. It is evident that study of functional roles for STIM molecules is clearly ahead of studies of specific ORAI family members in all innate cell types, and that studies of CRAC channels in innate cells are not nearly as advanced as studies in lymphocytes. However, taken together, evidence from both STIM calcium sensors and ORAI channels in innate cells indicates that deficiency of STIM and ORAI proteins tends not to affect the development of any innate cell lineage, but certainly affects their function, in particular activation of the neutrophil oxidase and mast cell activation via IgE receptors. Furthermore, there are clearly hints that therapeutic targeting of CRAC channels in innate cells offers a new approach to various inflammatory and allergic diseases.