title: TMEM110 regulates the maintenance and remodeling of mammalian ER-plasma membrane junctions competent for STIM-ORAI signaling.
abstract: The stromal interaction molecule (STIM)-ORAI calcium release-activated calcium modulator (ORAI) pathway 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, 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. However, little is known about proteins that organize ER-plasma membrane junctions for STIM-ORAI-dependent calcium signaling. Here, we report that an ER-resident membrane protein identified in a previous genome-wide RNAi screen, transmembrane protein 110 (TMEM110), regulates the long-term maintenance of ER-plasma membrane junctions and the short-term physiological remodeling of the junctions during store-dependent calcium signaling.
authors.affiliation: Division of Signalling and Gene Expression, La Jolla Institute for Allergy and Immunology, La Jolla, CA 92037;
authors.forename: Ariel
authors.initials: A
authors.lastname: Quintana
authors.affiliation: Division of Signalling and Gene Expression, La Jolla Institute for Allergy and Immunology, La Jolla, CA 92037;
authors.forename: Vangipurapu
authors.initials: V
authors.lastname: Rajanikanth
authors.affiliation: Division of Signalling and Gene Expression, La Jolla Institute for Allergy and Immunology, La Jolla, CA 92037;
authors.forename: Suzette
authors.initials: S
authors.lastname: Farber-Katz
authors.affiliation: Division of Signalling and Gene Expression, La Jolla Institute for Allergy and Immunology, La Jolla, CA 92037;
authors.forename: Aparna
authors.initials: A
authors.lastname: Gudlur
authors.affiliation: Division of Signalling and Gene Expression, La Jolla Institute for Allergy and Immunology, La Jolla, CA 92037;
authors.forename: Chen
authors.initials: C
authors.lastname: Zhang
authors.affiliation: Center for Translational Cancer Research, Institute of Biosciences and Technology, Texas A&M University Health Science Center, Houston, TX 77030;
authors.forename: Ji
authors.initials: J
authors.lastname: Jing
authors.affiliation: Center for Translational Cancer Research, Institute of Biosciences and Technology, Texas A&M University Health Science Center, Houston, TX 77030; Department of Medical Physiology, College of Medicine, Texas A&M University Health Science Center, Temple, TX 76504;
authors.forename: Yubin
authors.initials: Y
authors.lastname: Zhou
authors.affiliation: Division of Signalling and Gene Expression, La Jolla Institute for Allergy and Immunology, La Jolla, CA 92037; Department of Pharmacology and Moores Cancer Center, University of California, San Diego, La Jolla, CA 92037; Sanford Consortium for Regenerative Medicine, La Jolla, CA 92037 arao@liai.org phogan@liai.org.
authors.forename: Anjana
authors.initials: A
authors.lastname: Rao
authors.affiliation: Division of Signalling and Gene Expression, La Jolla Institute for Allergy and Immunology, La Jolla, CA 92037; arao@liai.org phogan@liai.org.
authors.forename: Patrick G
authors.initials: PG
authors.lastname: Hogan
mesh_terms: D015220:Calcium Channels / Q000378:metabolism*; D020013:Calcium Signaling; D015815:Cell Adhesion Molecules / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism; D002462:Cell Membrane / Q000378:metabolism / Q000648:ultrastructure; D004721:Endoplasmic Reticulum / Q000378:metabolism* / Q000648:ultrastructure; D006367:HeLa Cells; D006801:Humans; D019169:Jurkat Cells; D008565:Membrane Proteins / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D046529:Microscopy, Electron, Transmission; D009363:Neoplasm Proteins / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D000071740:ORAI1 Protein; D034622:RNA Interference; D011993:Recombinant Fusion Proteins / Q000235:genetics / Q000378:metabolism; D000071737:Stromal Interaction Molecule 1; D000071738:Stromal Interaction Molecule 2
chemical_list: D015220:Calcium Channels; D015815:Cell Adhesion Molecules; D008565:Membrane Proteins; D009363:Neoplasm Proteins; D000071740:ORAI1 Protein; C510746:ORAI1 protein, human; D011993:Recombinant Fusion Proteins; C103530:STIM1 protein, human; C513279:STIM2 protein, human; C000604313:STIMATE protein, human; D000071737:Stromal Interaction Molecule 1; D000071738:Stromal Interaction Molecule 2
keywords: CRAC channel; ORAI; STIM1; STIM2; store-operated calcium entry