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A Tale of two receptors
Ielyaas Cloete1, Juliana C Corrêa-Velloso2, Paula J Bartlett2
1Department of Mathematics, University of Auckland, Auckland 1142, New Zealand.
Journal of Theoretical Biology
|February 19, 2021
Summary
This study introduces a new computational model for calcium (Ca2+) oscillations in hepatocytes, revealing how phospholipase C (PLC) and protein kinase C (PKC) activity drive diverse responses to P2Y receptor stimulation.
Area of Science:
- Cellular Biology
- Biophysics
- Computational Biology
Background:
- Hepatocyte calcium (Ca2+) signaling exhibits a broad dynamic range.
- Agonist stimulation of P2Y receptors triggers diverse Ca2+ oscillation patterns.
Purpose of the Study:
- To develop a novel computational model of hepatocyte Ca2+ oscillations.
- To investigate the mechanisms underlying P2Y-activated Ca2+ oscillations.
- To explore the roles of IP3 receptor, phospholipase C (PLC), and protein kinase C (PKC) in regulating Ca2+ dynamics.
Main Methods:
- Development of a mathematical model simulating Ca2+ dynamics in hepatocytes.
- Incorporation of Ca2+-dependent regulation of the IP3 receptor (IP3R).
- Modeling of positive feedback from Ca2+ on PLC and P2Y receptor phosphorylation by PKC.
Main Results:
- The model successfully reproduces qualitatively diverse Ca2+ oscillations.
- It highlights the critical role of Ca2+ feedback mechanisms.
- PKC is identified as a key regulator controlling multiple cellular substrates.
Conclusions:
- The model provides insights into the mechanisms controlling P2Y-activated Ca2+ oscillations.
- Specific activities and intensities of PLC and PKC are proposed to explain observed oscillation diversity.
- This work advances understanding of calcium signaling regulation in hepatocytes.
Keywords:
IP(3)IP(3) receptorsModels of calcium oscillationsP2Y receptorsPhospholipase C (PLC)Protein Kinase C (PKC)Purinergic receptorsReceptor phosphorylationSignal transductionMore Related Videos
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