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

Ariel Quintana; Vangipurapu Rajanikanth; Suzette Farber-Katz; Aparna Gudlur; Chen Zhang; Ji Jing; Yubin Zhou; Anjana Rao; Patrick G Hogan

doi:10.1073/pnas.1521924112

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. Epub 2015 Dec 7.

Authors

Ariel Quintana¹, Vangipurapu Rajanikanth¹, Suzette Farber-Katz¹, Aparna Gudlur¹, Chen Zhang¹, Ji Jing², Yubin Zhou³, Anjana Rao⁴, Patrick G Hogan⁵

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.

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.

Publication types

Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't

MeSH terms

Calcium Channels / metabolism*
Calcium Signaling
Cell Adhesion Molecules / antagonists & inhibitors
Cell Adhesion Molecules / genetics
Cell Adhesion Molecules / metabolism
Cell Membrane / metabolism
Cell Membrane / ultrastructure
Endoplasmic Reticulum / metabolism*
Endoplasmic Reticulum / ultrastructure
HeLa Cells
Humans
Jurkat Cells
Membrane Proteins / antagonists & inhibitors
Membrane Proteins / genetics
Membrane Proteins / metabolism*
Microscopy, Electron, Transmission
Neoplasm Proteins / antagonists & inhibitors
Neoplasm Proteins / genetics
Neoplasm Proteins / metabolism*
ORAI1 Protein
RNA Interference
Recombinant Fusion Proteins / genetics
Recombinant Fusion Proteins / metabolism
Stromal Interaction Molecule 1
Stromal Interaction Molecule 2

Substances

Calcium Channels
Cell Adhesion Molecules
Membrane Proteins
Neoplasm Proteins
ORAI1 Protein
ORAI1 protein, human
Recombinant Fusion Proteins
STIM1 protein, human
STIM2 protein, human
STIMATE protein, human
Stromal Interaction Molecule 1
Stromal Interaction Molecule 2

Abstract

Publication types

MeSH terms

Substances

Grants and funding