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Title

Local cytosolic Ca2+ elevations are required for stromal interaction molecule 1 (STIM1) de-oligomerization and termination of store-operated Ca2+ entry

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Published in Journal of Biological Chemistry. 2011, vol. 286, no. 42, p. 36448-59
Abstract The Ca(2+) depletion of the endoplasmic reticulum (ER) activates the ubiquitous store-operated Ca(2+) entry (SOCE) pathway that sustains long-term Ca(2+) signals critical for cellular functions. ER Ca(2+) depletion initiates the oligomerization of stromal interaction molecules (STIM) that control SOCE activation, but whether ER Ca(2+) refilling controls STIM de-oligomerization and SOCE termination is not known. Here, we correlate the changes in free luminal ER Ca(2+) concentrations ([Ca(2+)](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 [Ca(2+)](ER) levels during store refilling than it oligomerized during store depletion. We then refilled ER stores without adding exogenous Ca(2+) using a membrane-permeable Ca(2+) chelator to provide a large reservoir of buffered Ca(2+). This procedure rapidly restored pre-stimulatory [Ca(2+)](ER) levels but did not trigger STIM1 de-oligomerization, the FRET signals remaining elevated as long as the external [Ca(2+)] remained low. STIM1 dissociation evoked by Ca(2+) readmission was prevented by SOC channel inhibition and was associated with cytosolic Ca(2+) elevations restricted to STIM1 puncta, indicating that Ca(2+) acts on a cytosolic target close to STIM1 clusters. These data indicate that the refilling of ER Ca(2+) stores is not sufficient to induce STIM1 de-oligomerization and that localized Ca(2+) elevations in the vicinity of assembled SOCE complexes are required for the termination of SOCE.
Keywords Calcium/metabolismChelating Agents/pharmacologyEndoplasmic Reticulum/genetics/metabolismFluorescence Resonance Energy Transfer/methodsHeLa CellsHumansMembrane Proteins/genetics/metabolismNeoplasm Proteins/genetics/metabolismProtein Multimerization/drug effects/physiology
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PMID: 21880734
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Article (Published version) (3.6 MB) - public document Free access
Structures
Research groups Signaux intracellulaires (210)
Canaux ioniques endothéliaux (828)
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(ISO format)
SHEN, Weiwei, FRIEDEN, Maud, DEMAUREX, Nicolas. Local cytosolic Ca2+ elevations are required for stromal interaction molecule 1 (STIM1) de-oligomerization and termination of store-operated Ca2+ entry. In: Journal of Biological Chemistry, 2011, vol. 286, n° 42, p. 36448-59. https://archive-ouverte.unige.ch/unige:21499

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Deposited on : 2012-06-06

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