Cross-linking of Orai1 channels by STIM proteins

This is the authors' abstract. We don't add key points for this paper.

Significance The work presents a unique understanding of the organization and function of two ubiquitously expressed proteins, central in generating calcium signals in all cell types. These are the intracellular calcium sensing “STIM” proteins, and the highly selective cell surface “Orai” calcium channels. We reveal that STIM proteins can cross-link Orai channels, resulting in a reorganized microenvironment within the membrane junctions in which they function, with important consequences in the generation of oscillatory calcium signals. Interestingly, we show a variant STIM protein widely expressed in cells functions to prevent the STIM–Orai cross-linking and clustering of channels. This provides important modulation of calcium signal generation and can serve to protect cells from overstimulation of the calcium signaling machinery.