8.A.65 The Endoplasmic Reticulum (ER)-Plasma Membrane (PM) Junctional Competence Regulator (TMEM110) Family
The stromal interaction molecule (STIM)-ORAI calcium release-activated calcium modulator (ORAI) pathway (TC# 1.A.52) controls store-dependent calcium entry, a major mechanism of physiological calcium signaling in mammalian cells. The core elements of the pathway are the regulatory protein STIM1, located in the endoplasmic reticulum (ER) membrane, the calcium channel ORAI1 in the plasma membrane (PM), and sites of close contact between the ER and the plasma membrane that permit the two proteins to interact. Research on calcium signaling has centered on STIM1, ORAI1, and a few proteins that directly modulate STIM-ORAI function. Proteins that organize ER-PM junctions for STIM-ORAI-dependent calcium signaling include an ER-resident membrane protein, transmembrane protein 110 (TMEM110). It regulates the long-term maintenance of ER-plasma membrane junctions and the short-term physiological remodeling of the junctions during store-dependent calcium signaling (Quintana et al. 2015).