PLC regulation: emerging pictures for molecular mechanisms
Abstract
Phosphoinositide-specific phospholipase C (PLC) enzymes are common signalling components linked to the activation of most cellular receptors. All PLC families are complex, modular, multi-domain proteins and together cover a broad spectrum of regulatory interactions, including direct binding to G protein subunits, small GTPases from Rho and Ras families, receptor and non-receptor tyrosine kinases and lipid components of cellular membranes. Recent structural determinations of PLC components and their complexes with regulatory proteins and direct mechanistic studies, together with earlier work, have provided the foundation to propose molecular mechanisms that stringently regulate PLC activity.
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PLCG2 mediates the hydrolysis of phosphatidylinositol 4,5-bisphosphate (PIP2) into inositol 1,4,5-trisphosphate (IP3) and diacylglycerol (DAG).
“PLCG2 associates with the membrane and mediates the hydrolysis of phosphatidylinositol 4, 5‐bisphosphate (PIP2) into two important second messengers: inositol 1, 4, 5‐trisphosphate (IP3) and diacylglycerol (DAG). 14 , 15”
From Alzheimer's disease–associated PLCG2 variants alter microglial state and function in human induced pluripotent stem cell–derived microglia‐like cells (2025) · cites this paper as [14]
PLCγ2 is a direct modulator of Ca2+ influx from the endoplasmic reticulum (ER) via its hydrolysis of PIP2, leading to the production of IP3, which then interacts with its receptor IP3R1.
“PLCγ2 is a direct modulator of Ca2+ influx from the endoplasmic reticulum (ER) via its hydrolysis of PIP2, leading to the production of IP3, which then interacts with its receptor IP3R1 [49].”
From Heterozygous expression of the Alzheimer’s disease-protective PLCγ2 P522R variant enhances Aβ clearance while preserving synapses (2022) · cites this paper as [49]
Upon activation, PLCγ2 hydrolyses the PM-inner-leaflet-localised lipid, PIP2, to produce inositol (1,4,5)-trisphosphate and diacylglycerol (DAG).
“Upon activation, PLCγ2 hydrolyses the PM-inner-leaflet-localised lipid, PIP2, to produce inositol (1,4,5)-trisphosphate and diacylglycerol (DAG) [75, 76].”
From TREM2/PLCγ2 signalling in immune cells: function, structural insight, and potential therapeutic modulation (2021) · cites this paper as [76]
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Ras Conformational Ensembles, Allostery, and Signaling
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“of IP3, which then interacts with its receptor IP3R1 [49].”
BackgroundPhospholipase C‐β1 potentiates glucose‐stimulated insulin secretion
Hwang, H.-J., Yang, Y. R., Kim, H. Y., Choi, Y., Park, K.-S., Lee, H., Ma, J. S., Yamamoto, M., Kim, J., Chae, Y. C., et al. (2019) · The FASEB Journal · doi:10.1096/fj.201802732rr · Cited by 20 · see citing works
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Bedford, L. M., Tutrow, K. D., Hooper, K., Messenger, E. J., Hernandez, M., Lamb, B. T., Meyer, J. S., Richardson, T. I., & Bissel, S. J. (2025) · Alzheimer's & Dementia · doi:10.1002/alz.70772 · Cited by 8 · see citing works
- Authors
- Bunney, T. D., & Katan, M.
- Affiliations
- Institute of Cancer Research (GB)
- Corresponding author
- Katan, Matilda
- Venue
- Trends in Biochemical Sciences
- Publisher
- Elsevier BV
- Published
- 2011-02
- Volume
- 36
- Issue
- 2
- Pages
- 88-96
- ISSN
- 0968-0004 (ISSN-L)
- OpenAlex
- W2120791660
- Cited by
- 182
- References
- 2
- Citations by year
- 2026: 3 · 2025: 2 · 2024: 5 · 2023: 5 · 2022: 10 · 2021: 8 · 2020: 10 · 2019: 11 · 2018: 9 · 2017: 7 · 2016: 13 · 2015: 16 · 2014: 13 · 2013: 24 · 2012: 29
- FWCI
- 1.93
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Trends in Biochemical Sciences (publishedVersion)
- PubMed (publishedVersion)
- UCL Discovery (University College London) (submittedVersion)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Protein Kinase Regulation and GTPase Signaling
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Receptor Mechanisms and Signaling
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Cellular transport and secretion
- Keywords
- phosphatidylinositol-specific phospholipase C, G protein subunits, Rho GTPases, Ras GTPase, tyrosine kinase, protein-protein interaction, enzyme activation mechanism
- MeSH terms
- Animals, Cell Membrane, Enzyme Activation, Humans, Models, Molecular, Signal Transduction, GTP-Binding Proteins, GTP Phosphohydrolases, Phosphoinositide Phospholipase C
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