Emergence of broad cytosolic Ca2+ oscillations in the absence of CRAC channels : A model for CRAC-mediated negative feedback on PLC and Ca2+ oscillations through PKC
Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved..
The role of Ca2+ release-activated Ca2+ (CRAC) channels mediated by ORAI isoforms in calcium signalling has been extensively investigated. It has been shown that the presence or absence of different isoforms has a significant effect on store-operated calcium entry (SOCE). Yoast et al. (2020) showed that, in addition to the reported narrow-spike oscillations (whereby cytosolic calcium decreases quickly after a sharp increase), ORAI1 knockout HEK293 cells were able to oscillate with broad-spike oscillations (whereby cytosolic calcium decreases in a prolonged manner after a sharp increase) when stimulated with a muscarinic agonist. This suggests that Ca2+ influx through ORAI-mediated CRAC channels negatively regulates the duration of Ca2+ oscillations. We hypothesise that, through the activation of protein kinase C (PKC), ORAI1 negatively regulates phospholipase C (PLC) activity to decrease inositol 1,4,5-trisphosphate (IP3) production and limit the duration of agonist-evoked Ca2+ oscillations. Based on this hypothesis, we construct a new mathematical model, which shows that the formation of broad-spike oscillations is highly dependent on the absence of ORAI1. Predictions of this model are consistent with the experimental results.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2024 |
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| Erschienen: |
2024 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:581 |
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| Enthalten in: |
Journal of theoretical biology - 581(2024) vom: 21. März, Seite 111740 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Lee, Lloyd [VerfasserIn] |
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| Links: |
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| Anmerkungen: |
Date Completed 19.02.2024 Date Revised 22.03.2024 published: Print-Electronic Citation Status MEDLINE |
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| doi: |
10.1016/j.jtbi.2024.111740 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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| 245 | 1 | 0 | |a Emergence of broad cytosolic Ca2+ oscillations in the absence of CRAC channels |b A model for CRAC-mediated negative feedback on PLC and Ca2+ oscillations through PKC |
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| 520 | |a Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved. | ||
| 520 | |a The role of Ca2+ release-activated Ca2+ (CRAC) channels mediated by ORAI isoforms in calcium signalling has been extensively investigated. It has been shown that the presence or absence of different isoforms has a significant effect on store-operated calcium entry (SOCE). Yoast et al. (2020) showed that, in addition to the reported narrow-spike oscillations (whereby cytosolic calcium decreases quickly after a sharp increase), ORAI1 knockout HEK293 cells were able to oscillate with broad-spike oscillations (whereby cytosolic calcium decreases in a prolonged manner after a sharp increase) when stimulated with a muscarinic agonist. This suggests that Ca2+ influx through ORAI-mediated CRAC channels negatively regulates the duration of Ca2+ oscillations. We hypothesise that, through the activation of protein kinase C (PKC), ORAI1 negatively regulates phospholipase C (PLC) activity to decrease inositol 1,4,5-trisphosphate (IP3) production and limit the duration of agonist-evoked Ca2+ oscillations. Based on this hypothesis, we construct a new mathematical model, which shows that the formation of broad-spike oscillations is highly dependent on the absence of ORAI1. Predictions of this model are consistent with the experimental results | ||
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a Research Support, N.I.H., Extramural | |
| 650 | 4 | |a Bifurcation analysis | |
| 650 | 4 | |a Broad-spike oscillations | |
| 650 | 4 | |a Calcium influx | |
| 650 | 4 | |a ORAI | |
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| 650 | 7 | |a Calcium Channels |2 NLM | |
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| 700 | 1 | |a Emrich, Scott |e verfasserin |4 aut | |
| 700 | 1 | |a Trebak, Mohamed |e verfasserin |4 aut | |
| 700 | 1 | |a Kirk, Vivien |e verfasserin |4 aut | |
| 700 | 1 | |a Sneyd, James |e verfasserin |4 aut | |
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