ArticleThe Journal of general physiology2013
Quantitative properties and receptor reserve of the DAG and PKC branch of G(q)-coupled receptor signaling.
Article in The Journal of general physiology, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 62 papers.
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Who cites it
62 citing papers in PubMed.
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- Neurovascular Signaling in the Perivascular Space: Biophysical Principles and Disruption in Hypertension.Hypertension (Dallas, Tex. : 1979) · 2026Review
- From lipid dynamics to precision predictions: A new approach methodology for precision modeling of phosphoinositide signaling.Journal of precision medicine (Amsterdam, Netherlands) · 2026Article
- The expanding landscape of the glucagon signaling network: mechanisms and outcomes.Endocrinology · 2026Review
- Comparative transcriptome profiling of electrical and controlled atmosphere stunning in finishing pigs.Food science of animal resources · 2026Article
- Synaptic transmission: Munc13 assembles onto PI(4,5)PProceedings of the National Academy of Sciences of the United States of America · 2026Article
- A Novel Weight Loss Mechanism of Hydroxysafflor Yellow A in Obese Mice: Involvement of Immune Inflammation via Prkcd, Btk, and Vav1 Genes in Adipose Tissue.Current pharmaceutical biotechnology · 2026Article
- PIPProceedings of the National Academy of Sciences of the United States of America · 2025Article
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- Structural and functional insights into α-actinin isoforms and their implications in cardiovascular disease.The Journal of general physiology · 2025Review
- Neuroprotection against beta-amyloid toxicity by the novel estrogen receptor modulator STX requires convergent signaling pathways.Frontiers in molecular neuroscience · 2025Article
- The role of neuropeptides in cutaneous wound healing: a focus on mechanisms and neuropeptide-derived treatments.Frontiers in bioengineering and biotechnology · 2024Review
- Diacylglycerol-dependent hexamers of the SNARE-assembling chaperone Munc13-1 cooperatively bind vesicles.Proceedings of the National Academy of Sciences of the United States of America · 2023Article
- Involvement of CaCellular and molecular neurobiology · 2023Article
- Biophysical physiology of phosphoinositide rapid dynamics and regulation in living cells.The Journal of general physiology · 2022Article
- Auriculocondylar syndrome 2 results from the dominant-negative action of PLCB4 variants.Disease models & mechanisms · 2022Article
- Fe-Curcumin Nanozyme-Mediated Reactive Oxygen Species Scavenging and Anti-Inflammation for Acute Lung Injury.ACS central science · 2022Article
- G-Protein Coupled Receptors (GPCRs): Signaling Pathways, Characterization, and Functions in Insect Physiology and Toxicology.International journal of molecular sciences · 2021Review
2 more citing papers are in PubMed but not listed here.
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3 authors.
Funding
Abstract
Gq protein-coupled receptors (GqPCRs) of the plasma membrane activate the phospholipase C (PLC) signaling cascade. PLC cleaves the membrane lipid phosphatidylinositol 4,5-bisphosphate (PIP2) into the second messengers diacylgycerol (DAG) and inositol 1,4,5-trisphosphate (IP3), leading to calcium release, protein kinase C (PKC) activation, and in some cases, PIP2 depletion. We determine the kinetics of each of these downstream endpoints and also ask which is responsible for the inhibition of KCNQ2/3 (KV7.2/7.3) potassium channels in single living tsA-201 cells. We measure DAG production and PKC activity by Förster resonance energy transfer-based sensors, and PIP2 by KCNQ2/3 channels. Fully activating endogenous purinergic receptors by uridine 5'triphosphate (UTP) leads to calcium release, DAG production, and PKC activation, but no net PIP2 depletion. Fully activating high-density transfected muscarinic receptors (M1Rs) by oxotremorine-M (Oxo-M) leads to similar calcium, DAG, and PKC signals, but PIP2 is depleted. KCNQ2/3 channels are inhibited by the Oxo-M treatment (85%) and not by UTP (<1%), indicating that depletion of PIP2 is required to inhibit KCNQ2/3 in response to receptor activation. Overexpression of A kinase-anchoring protein (AKAP)79 or calmodulin (CaM) does not increase KCNQ2/3 inhibition by UTP. From these results and measurements of IP3 and calcium presented in our companion paper (Dickson et al. 2013. J. Gen. Physiol. http://dx.doi.org/10.1085/jgp.201210886), we extend our kinetic model for signaling from M1Rs to DAG/PKC and IP3/calcium signaling. We conclude that calcium/CaM and PKC-mediated phosphorylation do not underlie dynamic KCNQ2/3 channel inhibition during GqPCR activation in tsA-201 cells. Finally, our experimental data provide indirect evidence for cleavage of PI(4)P by PLC in living cells, and our modeling revisits/explains the concept of receptor reserve with measurements from all steps of GqPCR signaling.
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