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Significance  Store-operated Ca 2+  entry (SOCE) links Ca 2+  release from endoplasmic reticulum (ER) to Ca 2+  entry across the plasma membrane (PM). SOCE is unusual in requiring interaction between proteins in different membranes. STIM1, when it senses loss of ER Ca 2+ , unfurls domains that interact with Orai1 PM Ca 2+  channels. The stoichiometry of the SOCE complex is contentious, but it determines the regulation and functional consequences of SOCE. We show that native complexes are likely to comprise a single Orai1 channel and a few STIM1 dimers, too few to cluster Orai1 channels. We suggest that SOCE may be digitally regulated by local ER depletion, and that local SOCE-evoked Ca 2+  fluxes are small enough to allow substantial intracellular redistribution of Ca 2+  through ER tunnels.

The store-operated Ca 2+ entry complex comprises a small cluster of STIM1 associated with one Orai1 channel

The store-operated Ca ²⁺ entry complex comprises a small cluster of STIM1 associated with one Orai1 channel