Orai3 and Orai1 are essential for CRAC channel function and metabolic reprogramming in B cells

Emrich, S. M.; Yoast, R. E.; Zhang, X.; Fike, A. J.; Wang, Y.-H.; Bricker, K. N.; Tao, A.; Xin, P.; Walter, V.; Johnson, M. T.; Pathak, T.; Straub, A. C.; Feske, S.; Rahman, Z.; Trebak, M.

doi:10.1101/2022.05.06.490918

bioRxiv · 10.1101/2022.05.06.490918

Orai3 and Orai1 are essential for CRAC channel function and metabolic reprogramming in B cells

Emrich, S. M.·Yoast, R. E.·Zhang, X.·Fike, A. J.·Wang, Y.-H.·Bricker, K. N.·Tao, A.·Xin, P.·Walter, V.·Johnson, M. T.·Pathak, T.·Straub, A. C.·Feske, S.·Rahman, Z.·Trebak, M.

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Abstract

The essential role of store-operated Ca2+ entry (SOCE) through Ca2+ release-activated Ca2+ (CRAC) channels in T cells is well established. In contrast, the contribution of individual Orai isoforms to SOCE and their downstream signaling functions in B cells are poorly understood. Here, we demonstrate changes in expression of Orai isoforms in response to B cell activation. We show that Orai3 and Orai1 are essential components of native CRAC channels in B cells and are critical for primary B cell proliferation and survival. The combined loss of Orai1 and Orai3 strongly impairs SOCE, nuclear factor for activated T cells (NFAT) activation, mitochondrial respiration, glycolysis, and the metabolic reprogramming of B cells in response to antigenic stimulation. Our results clarify the molecular composition and cellular functions of SOCE in B lymphocytes.

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Emrich, S. M., Yoast, R. E., Zhang, X., Fike, A. J., Wang, Y.-H., Bricker, K. N., Tao, A., Xin, P., Walter, V., Johnson, M. T., Pathak, T., Straub, A. C., Feske, S., Rahman, Z., Trebak, M.. 2022-05-06. Orai3 and Orai1 are essential for CRAC channel function and metabolic reprogramming in B cells. https://doi.org/10.1101/2022.05.06.490918

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