Is hydrogen ion (H+) the real second messenger in calcium signalling?
Abstract
Most second messengers have the acknowledged ability to mobilize the segregated Ca(2+) from intracellular stores, although the mechanisms of mobilization are unclear. To study this problem, the fact that inositol 1,4,5-trisphosphate, and six other known endogenous Ca(2+) mobilizers are acids, or acid-generating compounds, is highlighted. In physiological conditions, a newly generated acid releases H(+). The transient rise of H(+) in the cytosol may induce the lowering of pH, mobilization of bound Ca(2+), protein conformational rearrangement, store depletion, and Ca(2+) influx. Accordingly, a new description of the basic mechanism for signal transduction in non-excitable cells and the related consequences is put forward.
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Another consequence of PIP2 hydrolysis is the production of protons, which can lead to localised decreases in the juxtamembrane pH.
“Another consequence of PIP2 hydrolysis is the production of protons, which can lead to localised decreases in the juxtamembrane pH [80, 81].”
From TREM2/PLCγ2 signalling in immune cells: function, structural insight, and potential therapeutic modulation (2021) · cites this paper as [81]
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Magno, L., Bunney, T. D., Mead, E., Svensson, F., & Bictash, M. N. (2021) · Molecular Neurodegeneration · doi:10.1186/s13024-021-00436-5 · Cited by 64 · see citing works
- Authors
- Molinari, G.
- Corresponding author
- Molinari, Giuliano
- ORCID
- Molinari, Giuliano
- Venue
- Cellular Signalling
- Publisher
- Elsevier BV
- Published
- 2015-07
- Volume
- 27
- Issue
- 7
- Pages
- 1392-1397
- ISSN
- 0898-6568 (ISSN-L)
- OpenAlex
- W1979862341
- Cited by
- 13
- References
- 0
- Citations by year
- 2025: 1 · 2024: 5 · 2023: 2 · 2022: 1 · 2021: 2 · 2020: 1 · 2016: 1
- FWCI
- 0.25
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Cellular Signalling (publishedVersion)
- PubMed (publishedVersion)
- Funders
- University of California
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Physiology › Calcium signaling and nucleotide metabolism
- Life Sciences › Neuroscience › Sensory Systems › Ion Channels and Receptors
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Protein Kinase Regulation and GTPase Signaling
- Keywords
- hydrogen ions, second messengers, calcium signaling, inositol 1,4,5-trisphosphate, intracellular calcium stores, acidification, intracellular pH, store depletion, calcium influx, signal transduction, protein conformational change
- MeSH terms
- Cyclic AMP, Adenosine Triphosphate, Cytosol, Humans, Hydrogen-Ion Concentration, Lysophospholipids, NADP, Sphingosine, Second Messenger Systems, Inositol 1,4,5-Trisphosphate, Calcium Signaling
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