2. Academic Validation
  3. TMEM110 regulates the maintenance and remodeling of mammalian ER-plasma membrane junctions competent for STIM-ORAI signaling

TMEM110 regulates the maintenance and remodeling of mammalian ER-plasma membrane junctions competent for STIM-ORAI signaling

  • Proc Natl Acad Sci U S A. 2015 Dec 22;112(51):E7083-92. doi: 10.1073/pnas.1521924112.
Ariel Quintana 1,  Vangipurapu Rajanikanth 1,  Suzette Farber-Katz 1,  Aparna Gudlur 1,  Chen Zhang 1,  Ji Jing 2,  Yubin Zhou 3,  Anjana Rao 4,  Patrick G Hogan 5
Affiliations

Affiliations

  • 1 Division of Signalling and Gene Expression, La Jolla Institute for Allergy and Immunology, La Jolla, CA 92037;
  • 2 Center for Translational Cancer Research, Institute of Biosciences and Technology, Texas A&M University Health Science Center, Houston, TX 77030;
  • 3 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;
  • 4 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.
  • 5 Division of Signalling and Gene Expression, La Jolla Institute for Allergy and Immunology, La Jolla, CA 92037; arao@liai.org phogan@liai.org.
PMID: 26644574 DOI: 10.1073/pnas.1521924112
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.

Keywords

CRAC channel; ORAI; STIM1; STIM2; store-operated calcium entry.

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