EPIC3, a novel Ca2+ indicator located at the cell cortex and in microridges, detects high Ca2+ subdomains during Ca2+ influx and phagocytosis

Roberts, Rhiannon E.; Vervliet, Tim; Bultynck, Geert; Parys, Jan B.; Hallett, Maurice Bartlett

doi:10.1016/j.ceca.2020.102291

Cited by 5 publications

(5 citation statements)

References 38 publications

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“…The earliest report of such a Ca 2+ cloud localised to near the phagosome [32] is usually dismissed as almost certainly an optical artefact caused by the thinner cytoplasm around the pseudopodia that increased the excitation and efficiency in that area [17]. However, the phagosome itself may be a source of Ca 2+ that adds to or generates periphagosomal Ca 2+ events such as Ca 2+ hotspots [9,10].…”

Section: Discussionmentioning

confidence: 99%

“…Human neutrophils, isolated from the blood of healthy volunteers who had given informed consent, as described previously [10], were suspended in Krebs medium (NaCl 120 mM, KCl, 4.9 mM KH 2 PO 4 , 1.2 mM MgSO 4 , 1.2 mM CaCl 2 , 1.3 mM, HEPES 25 mM, and bovine serum albumin 0.1% adjusted to pH 7.4 with NaOH).…”

Section: Cell Preparationmentioning

confidence: 99%

“…Ca 2+ signalling within these cells involves both Ca 2+ influx from the extracellular environment and the release from stored Ca 2+ from within the cell [8]. Hotspots of Ca 2+ in the cytosol near the closed phagosome have also been reported in some phagocytic cells such as mouse embryonic fibroblasts and dHL60 cells [9] and RAW 264.7 cells [10]. It is suggested that these Ca 2+ microdomains (hotspots) arise from "leaky" interactions of STIM-1 on the endoplasmic reticulum (ER), the Ca 2+ storage organelle with channels on the phagosomal membrane [9].…”

Section: Introductionmentioning

confidence: 95%

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Intraphagosomal Free Ca2+ Changes during Phagocytosis

Dewitt,

Green,

Laffafian

et al. 2024

IJMS

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Phagocytosis (and endocytosis) is an unusual cellular process that results in the formation of a novel subcellular organelle, the phagosome. This phagosome contains not only the internalised target of phagocytosis but also the external medium, creating a new border between extracellular and intracellular environments. The boundary at the plasma membrane is, of course, tightly controlled and exploited in ionic cell signalling events. Although there has been much work on the control of phagocytosis by ions, notably, Ca2+ ions influxing across the plasma membrane, increasing our understanding of the mechanism enormously, very little work has been done exploring the phagosome/cytosol boundary. In this paper, we explored the changes in the intra-phagosomal Ca2+ ion content that occur during phagocytosis and phagosome formation in human neutrophils. Measuring Ca2+ ion concentration in the phagosome is potentially prone to artefacts as the intra-phagosomal environment experiences changes in pH and oxidation. However, by excluding such artefacts, we conclude that there are open Ca2+ channels on the phagosome that allow Ca2+ ions to “drain” into the surrounding cytosol. This conclusion was confirmed by monitoring the translocation of the intracellularly expressed YFP-tagged C2 domain of PKC-γ. This approach marked regions of membrane at which Ca2+ influx occurred, the earliest being the phagocytic cup, and then the whole cell. This paper therefore presents data that have novel implications for understanding phagocytic Ca2+ signalling events, such as peri-phagosomal Ca2+ hotspots, and other phenomena.

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Section: Discussionmentioning

confidence: 99%

Section: Cell Preparationmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 95%

See 1 more Smart Citation

Intraphagosomal Free Ca2+ Changes during Phagocytosis

Dewitt,

Green,

Laffafian

et al. 2024

IJMS

Self Cite

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“…[47,86,123,157] Activation of Ca 2+ -dependent cytoplasmic proteins PFT-induced Ca 2+ influx activates calpains, calmodulin, calcineurin, PKC and phospholipase A2 Refs. [48,[113][114][115][116]138,[158][159][160][161][162] Alteration in Ca 2+ homeostasis activates calpains, calmodulin, PKC and phospholipase A2 Refs. [47,125,143,155,156,[163][164][165] Cell Death PFTs induce: Necrosis Necroptosis Apoptosis Pyroptosis Refs.…”

Section: Demonstrated With Inhibitorsmentioning

confidence: 99%

“…Ca 2+ -dependent cytoplasmic proteins, if activated, are very sensitive sensors of alterations in Ca 2+ homeostasis, and thus of the presence of pores, alterations in the Ca 2+ channels of the endoplasmic reticulum, and/or alterations in the Ca 2+ channels in lysosomes. In fact, PFTs activate calpains, calmodulin, calcineurin, PKC, and phospholipase [ 114 , 158 , 159 , 160 , 161 , 162 ].…”

Section: Comparison Between Pft and Tcd Propertiesmentioning

confidence: 99%

Role of the Alteration in Calcium Homeostasis in Cell Death Induced by Clostridioides difficile Toxin A and Toxin B

Fettucciari

Dini

Marconi

et al. 2023

Biology

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Clostridioides difficile (C. difficile), responsible for 15–25% of gastrointestinal infections, causes health problems mainly due to the toxic activity of toxins A and B (Tcds). These are responsible for its clinical manifestations, including diarrhea, pseudomembranous colitis, toxic megacolon and death, with a mortality of 5–30% in primary infection, that increase following relapses. Studies on Tcd-induced cell death have highlighted a key role of caspases, calpains, and cathepsins, with involvement of mitochondria and reactive oxygen species (ROS) in a complex signaling pathway network. The complex response in the execution of various types of cell death (apoptosis, necrosis, pyroptosis and pyknosis) depends on the amount of Tcd, cell types, and Tcd receptors involved, and could have as initial/precocious event the alterations in calcium homeostasis. The entities, peculiarities and cell types involved in these alterations will decide the signaling pathways activated and cell death type. Calcium homeostasis alterations can be caused by calcium influx through calcium channel activation, transient intracellular calcium oscillations, and leakage of calcium from intracellular stores. These increases in cytoplasmic calcium have important effects on all calcium-regulated molecules, which may play a direct role in several cell death types and/or activate other cell death effectors, such as caspases, calpains, ROS and proapoptotic Bcl-2 family members. Furthermore, some support for the possible role of the calcium homeostasis alteration in Tcd-induced cell death originates from the similarity with cytotoxic effects that cause pore-forming toxins, based mainly on calcium influx through plasma membrane pores.

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TRPM2 - An adjustable thermostat

Bartók,

Csanády

2024

Cell Calcium

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EPIC3, a novel Ca2+ indicator located at the cell cortex and in microridges, detects high Ca2+ subdomains during Ca2+ influx and phagocytosis

Cited by 5 publications

References 38 publications

Intraphagosomal Free Ca2+ Changes during Phagocytosis

Intraphagosomal Free Ca2+ Changes during Phagocytosis

Role of the Alteration in Calcium Homeostasis in Cell Death Induced by Clostridioides difficile Toxin A and Toxin B

TRPM2 - An adjustable thermostat

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