The STIM1-ORAI1 microdomain

The regulatory protein STIM1 controls gating of the Ca2+ channel ORAI1 by a direct protein-protein interaction. Because STIM1 is anchored in the ER membrane and ORAI1 is in the plasma membrane, the STIM-ORAI pathway can support Ca2+ influx only where the two membranes come into close apposition, effectively demarcating a microdomain for Ca2+ signalling. This review begins with a brief summary of the STIM-ORAI pathway of store-operated Ca2+ influx, then turns to the special geometry of the STIM-ORAI microdomain and the expected characteristics of the microdomain Ca2+ signal. A final section of the review seeks to place the STIM-ORAI microdomain into a broader context of cellular Ca2+ signalling.