ArticleJournal of cell science2011
Stimulated association of STIM1 and Orai1 is regulated by the balance of PtdIns(4,5)P₂ between distinct membrane pools.
Article in Journal of cell science, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 63 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Who cites it
63 citing papers in PubMed, 95 citations in OpenAlex.
- DHHC21 is a STIM1 protein S-acyltransferase that modulates immune function in vivo.Journal of cell science · 2026Article
- Glycosphingolipids regulate phosphatidylserine transport machinery that operates at ER-PM contact sites.Nature communications · 2026Article
- Calcium Signaling Dysregulation in Diabetic Cardiomyopathy: Roles of STIM and Orai Channels.Handbook of experimental pharmacology · 2026Review
- DHHC21 is a STIM1 protein S-acyltransferase that modulates immune functionbioRxiv : the preprint server for biology · 2025Article
- Nanoscale clustering and dynamics of phosphatidylinositol 4,5-bisphosphate in an immune cell model.Biophysical journal · 2025Article
- Article
- Roles of Cholesterol and PtdIns(4,5)PAdvances in experimental medicine and biology · 2023Review
- Regulatory mechanisms controlling store-operated calcium entry.Frontiers in physiology · 2023Review
- CRAC and SK Channels: Their Molecular Mechanisms Associated with Cancer Cell Development.Cancers · 2022Review
- Similarities and Differences between the Orai1 Variants: Orai1α and Orai1β.International journal of molecular sciences · 2022Review
- LIPID transfer proteins regulate store-operated calcium entry via control of plasma membrane phosphoinositides.Cell calcium · 2022Article
- A palmitoylation code controls PI4KIIIα complex formation and PI(4,5)P2 homeostasis at the plasma membrane.Journal of cell science · 2022Article
- The Role of Lipids in CRAC Channel Function.Biomolecules · 2022Review
- STIM and Orai Mediated Regulation of Calcium Signaling in Age-Related Diseases.Frontiers in aging · 2022Review
- Orai1 Boosts SK3 Channel Activation.Cancers · 2021Article
- Regulation of Store-Operated CaCells · 2021Review
- Endoplasmic Reticulum-Plasma Membrane Contact Sites as an Organizing Principle for Compartmentalized Calcium and cAMP Signaling.International journal of molecular sciences · 2021Review
- Cross-Talk Between the Adenylyl Cyclase/cAMP Pathway and CaReviews of physiology, biochemistry and pharmacology · 2021Review
- ORAI1 CaFrontiers in cell and developmental biology · 2021Review
- PHOSPHOINOSITIDES AND CALCIUM SIGNALING. A MARRIAGE ARRANGED IN ER-PM CONTACT SITES.Current opinion in physiology · 2020Article
3 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
6 authors at 1 institution in 1 country.
Funding
Abstract
We have previously shown that PIP5KIβ and PIP5KIγ generate functionally distinct pools of phosphatidylinositol 4,5-bisphosphate [PtdIns(4,5)P(2)] important for antigen-stimulated Ca(2+) entry in mast cells. In the present study, we find that association of the endoplasmic reticulum (ER) Ca(2+) sensor, STIM1, and the store-operated Ca(2+) channel, Orai1, stimulated by thapsigargin-mediated ER store depletion, is enhanced by overexpression of PIP5KIβ and inhibited by overexpression of PIP5KIγ. These different PIP5KI isoforms cause differential enhancement of PtdIns(4,5)P(2) in detergent-resistant membrane (DRM) fractions, which comprise ordered lipid regions, and detergent-solubilized membrane (DSM) fractions, which comprise disordered lipid regions. Consistent with these results, the inositol 5-phosphatase L10-Inp54p, which is targeted to ordered lipids, decreases PtdIns(4,5)P(2) in the DRM fraction and inhibits thapsigargin-stimulated STIM1-Orai1 association and store-operated Ca(2+) entry, whereas the inositol 5-phosphatase S15-Inp54p, which is targeted to disordered lipids, decreases PtdIns(4,5)P(2) in the DSM fraction and enhances STIM1-Orai1 association. Removal of either the STIM1 C-terminal polylysine sequence (amino acids 677-685) or an N-terminal polyarginine sequence in Orai1 (amino acids 28-33) eliminates this differential sensitivity of STIM1-Orai1 association to PtdIns(4,5)P(2) in the distinctive membrane domains. Our results are consistent with a model of PtdIns(4,5)P(2) balance, in which store-depletion-stimulated STIM1-Orai1 association is positively regulated by the ordered lipid pool of PtdIns(4,5)P(2) and negatively regulated by PtdIns(4,5)P(2) in disordered lipid domains.
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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.