Omnitemporal choreographies of all five STIM/Orai and IP₃Rs underlie the complexity of mammalian Ca²⁺ signaling.

ABSTRACT: Stromal-interaction molecules (STIM1/2) sense endoplasmic reticulum (ER) Ca²⁺ depletion and activate Orai channels. However, the choreography of interactions between native STIM/Orai proteins under physiological agonist stimulation is unknown. We show that the five STIM1/2 and Orai1/2/3 proteins are non-redundant and function together to ensure the graded diversity of mammalian Ca²⁺ signaling. Physiological Ca²⁺ signaling requires functional interactions between STIM1/2, Orai1/2/3, and IP₃Rs, ensuring that receptor-mediated Ca²⁺ release is tailored to Ca²⁺ entry and nuclear factor of activated T cells (NFAT) activation. The N-terminal Ca²⁺-binding ER-luminal domains of unactivated STIM1/2 inhibit IP₃R-e

SUBMITTER: Emrich SM 

PROVIDER: S-EPMC7968378 | biostudies-literature | 2021 Mar

REPOSITORIES: biostudies-literature