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Significance Store-operated calcium entry (SOCE) is a widespread, essential signaling mechanism for cellular functions in both invertebrates and vertebrates and is controlled by two membrane proteins, STIM in the endoplasmic reticulum (ER) and Orai, in the plasma membrane (PM). How these proteins residing in two different compartments have evolved to interact with each other has not been elucidated. We show thatCaenorhabditis elegans has a distinct mechanism of SOCE in which the 2–3 loop is regulated by STIM1 and the N and C termini of Orai1 by intramolecular interaction, differing from the previously reported mechanism of human SOCE. Therefore our studies suggest that, while the STIM–Orai interaction has been conserved from invertebrates to mammals, the gating mechanism for Orai has evolved considerably.

Distinct gating mechanism of SOC channel involving STIM–Orai coupling and an intramolecular interaction of Orai in Caenorhabditis elegans