Note to users. If you're seeing this message, it means that your browser cannot find this page's style/presentation instructions -- or possibly that you are using a browser that does not support current Web standards. Find out more about why this message is appearing, and what you can do to make your experience of our site the best it can be.
Sci. Signal., 16 November 2010
Vol. 3, Issue 148, p. ra82
[DOI: 10.1126/scisignal.2001122]
RESEARCH ARTICLES
Editor's Summary
An Intramolecular STIM1 Inhibitor
Loss of Ca2+ from stores within the endoplasmic reticulum (ER) elicits translocation of STIM1 (stromal interacting molecule 1), a transmembrane ER protein, to a region of the ER near the plasma membrane, enabling its interaction with the Orai1 channel. This interaction leads to Orai1 activation—and thereby Ca2+ influx to elicit intracellular Ca2+ signals and replenish the depleted stores. In an exploration of the mechanisms involved in switching STIM1 from the inactive "resting" form found in cells with replete Ca2+ stores to the active form, Korzeniowski et al. identified a region of the STIM1 cytoplasmic domain required for maintenance of its inactive state and noted its resemblance to a region of Orai1 implicated in its interaction with STIM1. Mutational analysis, in combination with Förster resonance energy transfer and Ca2+ imaging, led them to propose a model in which this region acted as a decoy to block the ability of STIM1 to bind to and activate Orai1.
Citation: M. K. Korzeniowski, I. M. Manjarrés, P. Varnai, T. Balla, Activation of STIM1-Orai1 Involves an Intramolecular Switching Mechanism. Sci. Signal.3, ra82 (2010).
The editors suggest the following Related Resources on Science sites:
In Science Signaling
RESEARCH ARTICLES
Arti V. Shinde, Rajender K. Motiani, Xuexin Zhang, Iskandar F. Abdullaev, Alejandro P. Adam, José C. González-Cobos, Wei Zhang, Khalid Matrougui, Peter A. Vincent, and Mohamed Trebak (19 March 2013) Sci. Signal.6 (267), ra18.
[DOI: 10.1126/scisignal.2003425] |Editor's Summary »|Abstract »|Full Text »|PDF »|Supplementary Materials »
PERSPECTIVES
Brad S. Rothberg, Youjun Wang, and Donald L. Gill (19 March 2013) Sci. Signal.6 (267), pe9.
[DOI: 10.1126/scisignal.2003971] |Abstract »|Full Text »|PDF »
EDITORS' CHOICE
Valda Vinson (11 December 2012) Sci. Signal.5 (254), ec321.
[DOI: 10.1126/scisignal.2003851] |Abstract »
EDITORS' CHOICE
Nancy R. Gough (14 February 2012) Sci. Signal.5 (211), ec48.
[DOI: 10.1126/scisignal.2002954] |Abstract »
THIS ARTICLE HAS BEEN CITED BY OTHER ARTICLES:
Orai Channel Pore Properties and Gating by STIM: Implications from the Orai Crystal Structure.
The endocannabinoid N-arachidonoyl glycine (NAGly) inhibits store-operated Ca2+ entry by preventing STIM1-Orai1 interaction.
A. T. Deak, L. N. Groschner, M. R. Alam, E. Seles, A. I. Bondarenko, W. F. Graier, and R. Malli (2013)
J. Cell Sci.
126, 879-888
|Abstract »|Full Text »|PDF »
Anti-Hepatitis C Virus Activity and Toxicity of Type III Phosphatidylinositol-4-Kinase Beta Inhibitors.
M. J. LaMarche, J. Borawski, A. Bose, C. Capacci-Daniel, R. Colvin, M. Dennehy, J. Ding, M. Dobler, J. Drumm, L. A. Gaither, et al. (2012)
Antimicrob. Agents Chemother.
56, 5149-5156
|Abstract »|Full Text »|PDF »
cAMP Induces Stromal Interaction Molecule 1 (STIM1) Puncta but neither Orai1 Protein Clustering nor Store-operated Ca2+ Entry (SOCE) in Islet Cells.
G. Tian, A. V. Tepikin, A. Tengholm, and E. Gylfe (2012)
J. Biol. Chem.
287, 9862-9872
|Abstract »|Full Text »|PDF »
Hypoxia-induced Acidosis Uncouples the STIM-Orai Calcium Signaling Complex.
S. Mancarella, Y. Wang, X. Deng, G. Landesberg, R. Scalia, R. A. Panettieri, K. Mallilankaraman, X. D. Tang, M. Madesh, and D. L. Gill (2011)
J. Biol. Chem.
286, 44788-44798
|Abstract »|Full Text »|PDF »
Store-Operated Calcium Channels: New Perspectives on Mechanism and Function.
Local Cytosolic Ca2+ Elevations Are Required for Stromal Interaction Molecule 1 (STIM1) De-oligomerization and Termination of Store-operated Ca2+ Entry.
W.-W. Shen, M. Frieden, and N. Demaurex (2011)
J. Biol. Chem.
286, 36448-36459
|Abstract »|Full Text »|PDF »
Molecular Determinants within N Terminus of Orai3 Protein That Control Channel Activation and Gating.
J. Bergsmann, I. Derler, M. Muik, I. Frischauf, M. Fahrner, P. Pollheimer, C. Schwarzinger, H. J. Gruber, K. Groschner, and C. Romanin (2011)
J. Biol. Chem.
286, 31565-31575
|Abstract »|Full Text »|PDF »
A Cytosolic STIM2 Preprotein Created by Signal Peptide Inefficiency Activates ORAI1 in a Store-independent Manner.
S. J. L. Graham, M. A. Dziadek, and L. S. Johnstone (2011)
J. Biol. Chem.
286, 16174-16185
|Abstract »|Full Text »|PDF »
Calcium Signaling by STIM and Orai: Intimate Coupling Details Revealed.
