STIM1 and STIM2 Proteins Differently Regulate Endogenous Store-operated Channels in HEK293 Cells

The endoplasmic reticulum calcium sensors stromal interaction molecules 1 and 2 (STIM1 and STIM2) are key modulators of store-operated calcium entry. Both these sensors play a major role in physiological functions in normal tissue and in pathology, but available data on native STIM2-regulated plasma...

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Bibliographic Details
Published in:The Journal of biological chemistry 2015-02, Vol.290 (8), p.4717-4727
Main Authors: Shalygin, Alexey, Skopin, Anton, Kalinina, Vera, Zimina, Olga, Glushankova, Lyuba, Mozhayeva, Galina N., Kaznacheyeva, Elena
Format: Article
Language:English
Subjects:
Calcium
Calcium - metabolism
Calcium Channel
Calcium Signaling - physiology
Cell Adhesion Molecules - genetics
Cell Adhesion Molecules - metabolism
Cell Biology
Endoplasmic Reticulum (ER)
HEK293
HEK293 Cells
Humans
Imin
Membrane Proteins - genetics
Membrane Proteins - metabolism
Neoplasm Proteins - genetics
Neoplasm Proteins - metabolism
Patch Clamp
Single Channel
SOC
STIM2
Stromal Interaction Molecule 1
Stromal Interaction Molecule 1 (STIM1)
Stromal Interaction Molecule 2
Stromal Interaction Molecule 2 (STIM2)
TRPC Cation Channels - genetics
TRPC Cation Channels - metabolism
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Summary:The endoplasmic reticulum calcium sensors stromal interaction molecules 1 and 2 (STIM1 and STIM2) are key modulators of store-operated calcium entry. Both these sensors play a major role in physiological functions in normal tissue and in pathology, but available data on native STIM2-regulated plasma membrane channels are scarce. Only a few studies have recorded STIM2-induced CRAC (calcium release-activated calcium) currents. On the other hand, many cell types display store-operated currents different from CRAC. The STIM1 protein regulates not only CRAC but also transient receptor potential canonical (TRPC) channels, but it has remained unclear whether STIM2 is capable of regulating store-operated non-CRAC channels. Here we present for the first time experimental evidence for the existence of endogenous non-CRAC STIM2-regulated channels. As shown in single-channel patch clamp experiments on HEK293 cells, selective activation of native STIM2 proteins or STIM2 overexpression results in store-operated activation of Imin channels, whereas STIM1 activation blocks this process. Changes in the ratio between active STIM2 and STIM1 proteins can switch the regulation of Imin channels between store-operated and store-independent modes. We have previously characterized electrophysiological properties of different Ca2+ influx channels coexisting in HEK293 cells. The results of this study show that STIM1 and STIM2 differ in the ability to activate these store-operated channels; Imin channels are regulated by STIM2, TRPC3-containing INS channels are induced by STIM1, and TRPC1-composed Imax channels are activated by both STIM1 and STIM2. These new data about cross-talk between STIM1 and STIM2 and their different roles in store-operated channel activation are indicative of an additional level in the regulation of store-operated calcium entry pathways. Background: STIM calcium sensors are key modulators of store-operated channels (SOCs). Results: Changes in the ratio of active STIM2/STIM1 switch Imin channel regulation between store-operated and store-independent modes. Conclusion: Endogenous SOCs are differently regulated by STIM1 and STIM2. Significance: Cross-talk between STIM1 and STIM2 and their different roles in channel activation are indicative of an additional level of SOC regulation.
ISSN:0021-9258
1083-351X
DOI:10.1074/jbc.M114.601856