ArticleScientific reports2015
Identification of key amino acid residues responsible for internal and external pH sensitivity of Orai1/STIM1 channels.
Article in Scientific reports, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers.
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Who cites it
21 citing papers in PubMed, 37 citations in OpenAlex.
- A Hidden Checkpoint: Bidirectional pH Remodeling of the Immunological Synapse in Cancer, Methods, and Therapeutic Opportunities.Journal of immunology research · 2026Review
- Searching for Mechanisms Underlying the Assembly of Calcium Entry Units: The Role of Temperature and pH.International journal of molecular sciences · 2023Article
- CaInternational journal of molecular sciences · 2022Review
- Development of Inhaled GABAACS pharmacology & translational science · 2022Article
- Highlighting the Multifaceted Role of Orai1 N-Terminal- and Loop Regions for Proper CRAC Channel Functions.Cells · 2022Review
- Isoform-Specific Properties of Orai Homologues in Activation, Downstream Signaling, Physiology and Pathophysiology.International journal of molecular sciences · 2021Review
- Lysosomal agents inhibit store-operated CaJournal of cell science · 2021Article
- Distinct pharmacological profiles of ORAI1, ORAI2, and ORAI3 channels.Cell calcium · 2020Article
- Triclosan disrupts immune cell function by depressing CaToxicology and applied pharmacology · 2020Article
- Orai channels: key players in CaCurrent opinion in physiology · 2020Article
- pH-Channeling in Cancer: How pH-Dependence of Cation Channels Shapes Cancer Pathophysiology.Cancers · 2020Review
- T-cells produce acidic niches in lymph nodes to suppress their own effector functions.Nature communications · 2020Article
- Effects of REDOX in Regulating and Treatment of Metabolic and Inflammatory Cardiovascular Diseases.Oxidative medicine and cellular longevity · 2020Review
- A novel GABAAmerican journal of physiology. Lung cellular and molecular physiology · 2019Article
- ORAI1 channel gating and selectivity is differentially altered by natural mutations in the first or third transmembrane domain.The Journal of physiology · 2019Article
- STIM1 promotes migration, phagosomal maturation and antigen cross-presentation in dendritic cells.Nature communications · 2017Article
- Regulation of Orai1/STIM1 mediated IScientific reports · 2017Article
- GABAAmerican journal of physiology. Lung cellular and molecular physiology · 2017Article
- Extracellular protons enable activation of the calcium-dependent chloride channel TMEM16A.The Journal of physiology · 2017Article
- Store-Operated CaCurrent molecular biology reports · 2017Review
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Authors and funding
7 authors at 1 institution in 1 country.
Funding
Abstract
Changes of intracellular and extracellular pH are involved in a variety of physiological and pathological processes, in which regulation of the Ca(2+) release activated Ca(2+) channel (I CRAC) by pH has been implicated. Ca(2+) entry mediated by I CRAC has been shown to be regulated by acidic or alkaline pH. Whereas several amino acid residues have been shown to contribute to extracellular pH (pHo) sensitivity, the molecular mechanism for intracellular pH (pHi) sensitivity of Orai1/STIM1 is not fully understood. By investigating a series of mutations, we find that the previously identified residue E106 is responsible for pHo sensitivity when Ca(2+) is the charge carrier. Unexpectedly, we identify that the residue E190 is responsible for pHo sensitivity when Na(+) is the charge carrier. Furthermore, the intracellular mutant H155F markedly diminishes the response to acidic and alkaline pHi, suggesting that H155 is responsible for pHi sensitivity of Orai1/STIM1. Our results indicate that, whereas H155 is the intracellular pH sensor of Orai1/STIM1, the molecular mechanism of external pH sensitivity varies depending on the permeant cations. As changes of pH are involved in various physiological/pathological functions, Orai/STIM channels may be an important mediator for various physiological and pathological processes associated with acidosis and alkalinization.
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