Local Cytosolic Ca2+ Elevations Are Required for Stromal Interaction Molecule 1 (STIM1) De-oligomerization and Termination of Store-operated Ca2+ Entry
| Autor: | Maud Frieden, Nicolas Demaurex, Wei-Wei Shen |
|---|---|
| Rok vydání: | 2011 |
| Předmět: |
Orai1
Store-operated Channels Endoplasmic Reticulum Biochemistry Ion Channels Protein Multimerization/drug effects/physiology 0302 clinical medicine Fluorescence Resonance Energy Transfer Ca2 entry Chelating Agents 0303 health sciences STIM1 Membrane Proteins/genetics/metabolism CRAC Calcium Imaging Neoplasm Proteins Signal Transduction inorganic chemicals Calcium/metabolism chemistry.chemical_element Calcium Biology Neoplasm Proteins/genetics/metabolism 03 medical and health sciences Humans Calcium Signaling Stromal Interaction Molecule 1 ddc:612 Molecular Biology 030304 developmental biology Calcium metabolism Fluorescence Resonance Energy Transfer/methods Endoplasmic reticulum Membrane Proteins Cell Biology Cytosol Förster resonance energy transfer Endoplasmic Reticulum (ER) Membrane protein chemistry Biophysics Endoplasmic Reticulum/genetics/metabolism Protein Multimerization Chelating Agents/pharmacology 030217 neurology & neurosurgery HeLa Cells |
| Zdroj: | The Journal of Biological Chemistry The Journal of biological chemistry Journal of Biological Chemistry, Vol. 286, No 42 (2011) pp. 36448-59 |
| ISSN: | 0021-9258 |
| DOI: | 10.1074/jbc.m111.269415 |
| Popis: | Background: STIM1 oligomerization upon endoplasmic reticulum (ER) Ca2+ depletion activates store-operated Ca2+ entry (SOCE) channels, but whether this mechanism is reversible is unknown. Results: STIM1 de-oligomerization upon ER Ca2+ refilling requires concomitant cytosolic Ca2+ elevations near STIM1 membrane clusters. Conclusion: Cytosolic Ca2+ elevations dissociate STIM1 oligomers during SOCE termination. Significance: Ca2+ acts on a cytosolic target to control the disassembly of STIM1 membrane clusters. The Ca2+ depletion of the endoplasmic reticulum (ER) activates the ubiquitous store-operated Ca2+ entry (SOCE) pathway that sustains long-term Ca2+ signals critical for cellular functions. ER Ca2+ depletion initiates the oligomerization of stromal interaction molecules (STIM) that control SOCE activation, but whether ER Ca2+ refilling controls STIM de-oligomerization and SOCE termination is not known. Here, we correlate the changes in free luminal ER Ca2+ concentrations ([Ca2+]ER) and in STIM1 oligomerization, using fluorescence resonance energy transfer (FRET) between CFP-STIM1 and YFP-STIM1. We observed that STIM1 de-oligomerized at much lower [Ca2+]ER levels during store refilling than it oligomerized during store depletion. We then refilled ER stores without adding exogenous Ca2+ using a membrane-permeable Ca2+ chelator to provide a large reservoir of buffered Ca2+. This procedure rapidly restored pre-stimulatory [Ca2+]ER levels but did not trigger STIM1 de-oligomerization, the FRET signals remaining elevated as long as the external [Ca2+] remained low. STIM1 dissociation evoked by Ca2+ readmission was prevented by SOC channel inhibition and was associated with cytosolic Ca2+ elevations restricted to STIM1 puncta, indicating that Ca2+ acts on a cytosolic target close to STIM1 clusters. These data indicate that the refilling of ER Ca2+ stores is not sufficient to induce STIM1 de-oligomerization and that localized Ca2+ elevations in the vicinity of assembled SOCE complexes are required for the termination of SOCE. |
| Databáze: | OpenAIRE |
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