Calcium Channels in Fc Receptor Signaling

Attout, Tarik; Floto, A.; Launay, Pierre

doi:10.1007/978-3-319-07911-0_5

Cited by 4 publications

(6 citation statements)

References 76 publications

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“…We speculate that in addition to participating in phagosome–lysosome fusion, that this change in cytosolic Ca 2+ concentration may act as a signal to change the activation state of macrophages. For example, this may lead to activation of calmodulin and effects on transcription factors controlling gene expression . Thus, we propose that Ca 2+ originating from lysosome‐stores may have a very important role in re‐programming macrophages after phagocytosis and that this depends on PIKfyve and TRPML1.…”

Section: Resultsmentioning

confidence: 90%

The Phosphoinositide‐Gated Lysosomal Ca²⁺ Channel, TRPML1, Is Required for Phagosome Maturation

Dayam

Sarić

Shilliday

et al. 2015

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Macrophages internalize and sequester pathogens into a phagosome.Phagosomes then sequentially fuse with endosomes and lysosomes, converting into degradative phagolysosomes. Phagosome maturation is a complex process that requires regulators of the endosomal pathway including the phosphoinositide lipids. Phosphatidylinositol-3-phosphate and phosphatidylinositol-3,5-bisphosphate (PtdIns(3,5)P 2 ), which respectively control early endosomes and late endolysosomes, are both required for phagosome maturation. Inhibition of PIKfyve, which synthesizes PtdIns(3,5)P 2 , blocked phagosome-lysosome fusion and abated the degradative capacity of phagosomes. However, it is not known how PIKfyve and PtdIns(3,5)P 2 participate in phagosome maturation. TRPML1 is a PtdIns

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Section: Resultsmentioning

confidence: 90%

The Phosphoinositide‐Gated Lysosomal Ca²⁺ Channel, TRPML1, Is Required for Phagosome Maturation

Dayam

Sarić

Shilliday

et al. 2015

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“…However, the variable calcium responses observed in hippocampal neurons are in agreement with the variability of calcium responses in immune cells, which range from isolated [Ca 2+ ] i transients to long-lasting oscillations and increased plateaus [ 83 , 84 ]. These variable calcium responses in immune cells are thought to be due to the diversity of FcγR subtypes expressed on these cells [ 34 , 35 , 85 , 86 ]. Thus, the considerable variability observed in the calcium response of hippocampal cell cultures to IgG-IC likely reflects differences in the relative expression of activating versus inhibitory FcγR isotypes within and between cell types in our culture system, an interpretation that was confirmed by our flow cytometry data (co-expression of FcγRIa and FcγRIIb on the surface of neurons and astrocytes).…”

Section: Discussionmentioning

confidence: 99%

Fc gamma receptors are expressed in the developing rat brain and activate downstream signaling molecules upon cross-linking with immune complex

Stamou

Grodzki

Oostrum

et al. 2018

J Neuroinflammation

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BackgroundExposure of the developing brain to immune mediators, including antibodies, is postulated to increase risk for neurodevelopmental disorders and neurodegenerative disease. It has been suggested that immunoglobulin G-immune complexes (IgG-IC) activate Fc gamma receptors (FcγR) expressed on neurons to modify signaling events in these cells. However, testing this hypothesis is hindered by a paucity of data regarding neuronal FcγR expression and function.MethodsFcγR transcript expression in the hippocampus, cortex, and cerebellum of neonatal male and female rats was investigated ex vivo and in mixed cultures of primary hippocampal and cortical neurons and astrocytes using quantitative PCR analyses. Expression at the protein level in mixed cultures of primary hippocampal and cortical neurons and astrocytes was determined by immunocytochemistry, western blotting, proteotype analysis, and flow cytometry. The functionality of these receptors was assessed by measuring changes in intracellular calcium levels, Erk phosphorylation, and IgG internalization following stimulation with IgG-immune complexes.ResultsFcgrIa, FcgrIIa, FcgrIIb, FcgrIIIa, and Fcgrt transcripts were detectable in the cortex, hippocampus, and cerebellum at postnatal days 1 and 7. These transcripts were also present in primary hippocampal and cortical cell cultures, where their expression was modulated by IFNγ. Expression of FcγRIa, FcγRIIb, and FcγRIIIa, but not FcγRIIa or FcRn proteins, was confirmed in cultured hippocampal and cortical neurons and astrocytes at the single cell level. A subpopulation of these cells co-expressed the activating FcγRIa and the inhibitory FcγRIIb. Functional analyses demonstrated that exposure of hippocampal and cortical cell cultures to IgG-IC increases intracellular calcium and Erk phosphorylation and triggers FcγR-mediated internalization of IgG.ConclusionsOur data demonstrate that developing neurons and astrocytes in the hippocampus and the cortex express signaling competent FcγR. These findings suggest that IgG antibodies may influence normal neurodevelopment or function via direct interactions with FcγR on non-immune cells in the brain.Electronic supplementary materialThe online version of this article (10.1186/s12974-017-1050-z) contains supplementary material, which is available to authorized users.

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“…We revealed candidate targets related to disease processes and showed their relationship with inflammation, immunity and stress related to the development and pathophysiology of asthma. For example, the Fc receptor signalling regulates allergic reactions and represents a potential therapeutic target . Steroid hormone with anti‐inflammatory and anti‐allergic effects is currently the main means to prevent and treat asthma.…”

Section: Discussionmentioning

confidence: 99%

Urine metabolic profiles in paediatric asthma

et al. 2019

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Background and objective: Asthma is a global problem and complex disease suited for metabolomic profiling. This study explored the candidate biomarkers specific to paediatric asthma and provided insights into asthmatic pathophysiology. Methods: Children (aged 6-11 years) meeting the criteria for healthy control (n = 29), uncontrolled asthma (n = 37) or controlled asthma (n = 43) were enrolled. Gas chromatography-mass spectrometry was performed on urine samples of the patients to explore the different types of metabolite profile in paediatric asthma. Additionally, we employed a comprehensive strategy to elucidate the relationship between significant metabolites and asthma-related genes. Results: We identified 51 differential metabolites mainly related to dysfunctional amino acid, carbohydrate and purine metabolism. A combination of eight candidate metabolites, including uric acid, stearic acid, threitol, acetylgalactosamine, heptadecanoic acid, aspartic acid, xanthosine and hypoxanthine (adjusted P < 0.05 and fold-change >1.5 or <0.67), showed excellent discriminatory performance for the presence of asthma and the differentiation of poor-controlled or well-controlled asthma, and area under the curve values were >0.97 across groups. Enrichment analysis based on these targets revealed that the Fc receptor, intracellular steroid hormone receptor signalling pathway, DNA damage and fibroblast proliferation were involved in inflammation, immunity and stress-related biological progression of paediatric asthma. Conclusion: Metabolomic analysis of patient urine combined with network-biology approaches allowed discrimination of asthma profiles and subtypes according to the metabolic patterns. The results provided insight into the potential mechanism of paediatric asthma.We investigated metabolic profiles of paediatric asthma patients to identify asthma-specific biomarkers in urine. A combination of eight metabolites showed excellent discrimination across groups. Enrichment analysis identified complex biological processes associated with immunity, inflammation, oxidative stress and DNA damage. These approaches enabled discrimination between asthma stages and elucidate its mechanisms.

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Calcium Channels in Fc Receptor Signaling

Cited by 4 publications

References 76 publications

The Phosphoinositide‐Gated Lysosomal Ca²⁺ Channel, TRPML1, Is Required for Phagosome Maturation

The Phosphoinositide‐Gated Lysosomal Ca²⁺ Channel, TRPML1, Is Required for Phagosome Maturation

Fc gamma receptors are expressed in the developing rat brain and activate downstream signaling molecules upon cross-linking with immune complex

Urine metabolic profiles in paediatric asthma

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Calcium Channels in Fc Receptor Signaling

Cited by 4 publications

References 76 publications

The Phosphoinositide‐Gated Lysosomal Ca2+ Channel, TRPML1, Is Required for Phagosome Maturation

The Phosphoinositide‐Gated Lysosomal Ca2+ Channel, TRPML1, Is Required for Phagosome Maturation

Fc gamma receptors are expressed in the developing rat brain and activate downstream signaling molecules upon cross-linking with immune complex

Urine metabolic profiles in paediatric asthma

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Product

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The Phosphoinositide‐Gated Lysosomal Ca²⁺ Channel, TRPML1, Is Required for Phagosome Maturation

The Phosphoinositide‐Gated Lysosomal Ca²⁺ Channel, TRPML1, Is Required for Phagosome Maturation