ArticleProceedings of the National Academy of Sciences of the United States of America2012
Orai-STIM-mediated Ca2+ release from secretory granules revealed by a targeted Ca2+ and pH probe.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 31 papers.
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Who cites it
31 citing papers in PubMed, 50 citations in OpenAlex.
- The ion channels of endomembranes.Physiological reviews · 2024Review
- Regulation of autophagy by perilysosomal calcium: a new player in β-cell lipotoxicity.Experimental & molecular medicine · 2024Review
- Characterization of Endo-Lysosomal Cation Channels Using Calcium Imaging.Handbook of experimental pharmacology · 2023Article
- The evolution of organellar calcium mapping technologies.Cell calcium · 2022Review
- Lysosomal Calcium Channels in Autophagy and Cancer.Cancers · 2021Review
- Systematic Comparison of Vesicular Targeting Signals Leads to the Development of Genetically Encoded Vesicular Fluorescent ZnACS sensors · 2020Article
- Synthesis and Characterization of Store-Operated Calcium Entry Inhibitors Active in the Submicromolar Range.International journal of molecular sciences · 2020Article
- Single-nucleotide polymorphisms in Orai1 associated with atopic dermatitis inhibit protein turnover, decrease calcium entry and disrupt calcium-dependent gene expression.Human molecular genetics · 2020Article
- Signaling through CaCold Spring Harbor perspectives in biology · 2020Review
- Disease-associated mutations in Niemann-Pick type C1 alter ER calcium signaling and neuronal plasticity.The Journal of cell biology · 2019Article
- Release and uptake mechanisms of vesicular CaProtein & cell · 2019Review
- The Trans Golgi Region is a Labile Intracellular CaScientific reports · 2018Article
- Deletion of Orai1 leads to bone loss aggravated with aging and impairs function of osteoblast lineage cells.Bone reports · 2018Article
- Fluorescent Proteins for Investigating Biological Events in Acidic Environments.International journal of molecular sciences · 2018Review
- A voltage-dependent KThe Journal of cell biology · 2017Article
- TFEB-mediated increase in peripheral lysosomes regulates store-operated calcium entry.Scientific reports · 2017Article
- Exploring cells with targeted biosensors.The Journal of general physiology · 2017Review
- Genetically Encoded Fluorescent Indicators for Organellar Calcium Imaging.Biophysical journal · 2016Review
- Lysosomal Calcium in Neurodegeneration.Messenger (Los Angeles, Calif. : Print) · 2016Article
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Authors and funding
5 authors at 2 institutions in 2 countries.
Funding
Abstract
Secretory granules (SGs) sequester significant calcium. Understanding roles for this calcium and potential mechanisms of release is hampered by the difficulty of measuring SG calcium directly in living cells. We adapted the Förster resonance energy transfer-based D1-endoplasmic reticulum (ER) probe to develop a unique probe (D1-SG) to measure calcium and pH in secretory granules. It significantly localizes to SGs and reports resting free Ca(2+) of 69 ± 15 μM and a pH of 5.8. Application of extracellular ATP to activate P2Y receptors resulted in a slow monotonic decrease in SG Ca(2+) temporally correlated with the occurrence of store-operated calcium entry (SOCE). Further investigation revealed a unique receptor-mediated mechanism of calcium release from SGs that involves SG store-operated Orai channels activated by their regulator stromal interaction molecule 1 (STIM1) on the ER. SG Ca(2+) release is completely antagonized by a SOCE antagonist, by switching to Ca(2+)-free medium, and by overexpression of a dominant-negative Orai1(E106A). Overexpression of the CRAC activation domain (CAD) of STIM1 resulted in a decrease of resting SG Ca(2+) by ∼75% and completely abolished the ATP-mediated release of Ca(2+) from SGs. Overexpression of a dominant-negative CAD construct(CAD-A376K) induced no significant changes in SG Ca(2+). Colocalization analysis suggests that, like the plasma membrane, SG membranes also possess Orai1 channels and that during SG Ca(2+) release, colocalization between SGs and STIM1 increases. We propose Orai channel opening on SG membranes as a potential mode of calcium release from SGs that may serve to raise local cytoplasmic calcium concentrations and aid in refilling intracellular calcium stores of the ER and exocytosis.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.