Phospholipase C isozymes selectively couple to specific neurotransmitter receptors
Abstract
A variety of extracellular signals are transduced across the cell membrane by the enzyme phosphoinositide-specific phospholipase C-beta (PLC-beta) coupled with guanine-nucleotide-binding G proteins. There are four isoenzymes of PLC-beta, beta1-beta4, but their functions in vivo are not known. Here we investigate the role of PLC-beta1 and PLC-beta4 in the brain by generating null mutations in mice: we found that PLCbeta1-/- mice developed epilepsy and PLCbeta4-/- mice showed ataxia. We determined the molecular basis of these phenotypes and show that PLC-beta1 is involved in signal transduction in the cerebral cortex and hippocampus by coupling predominantly to the muscarinic acetylcholine receptor, whereas PLC-beta4 works through the metabotropic glutamate receptor in the cerebellum, illustrating how PLC-beta isoenzymes are used to generate different functions in the brain.
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PLCβ1 has been implicated in control of neuronal function and enhancement of glucose-stimulated insulin secretion in pancreatic β-cells downstream of specific GPCRs.
“Among many roles, ubiquitously expressed PLCβ1 enzyme has been implicated in control of neuronal function and the enhancement of glucose-stimulated insulin secretion in pancreatic β-cells downstream of specific GPCRs in these different cell types [36–40].”
From Phosphatidylinositol(4,5)bisphosphate: diverse functions at the plasma membrane (2020) · cites this paper as [36]
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- Authors
- Kim, D., Jun, K. S., Lee, S. B., Kang, N.-G., Min, D. S., Kim, Y.-H., Ryu, S. H., Suh, P.-G., & Shin, H.-S.
- Affiliations
- Pohang University of Science and Technology (KR)
- Inje University (KR)
- Corresponding author
- Shin, Hee-Sup
- Venue
- Nature
- Published
- 1997-09
- Volume
- 389
- Issue
- 6648
- Pages
- 290-293
- ISSN
- 0028-0836 (ISSN-L)
- 1476-4687
- OpenAlex
- W1597131590
- Cited by
- 305
- References
- 2
- Citations by year
- 2026: 4 · 2025: 5 · 2024: 6 · 2023: 4 · 2022: 13 · 2021: 9 · 2020: 5 · 2019: 10 · 2018: 6 · 2017: 7 · 2016: 10 · 2015: 15 · 2014: 9 · 2013: 14 · 2012: 14
- FWCI
- 4.16
- Type
- journal article
- Language
- en
- Open access
- closed
- Licence
- www.springer.com/tdm (tdm)
- Locations
- Nature (publishedVersion)
- PubMed (publishedVersion)
- RePEc: Research Papers in Economics (submittedVersion)
- Open Access System for Information Sharing (Pohang University of Science and Technology) (submittedVersion)
- Scholarworks@UNIST (Ulsan National Institute of Science and Technology) (submittedVersion)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Protein Kinase Regulation and GTPase Signaling
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Receptor Mechanisms and Signaling
- Keywords
- phospholipase C beta, PLCB1, isozyme specificity, G protein-coupled receptor signaling, muscarinic receptors, metabotropic glutamate receptors, epilepsy, ataxia, null mice, cerebral cortex, hippocampus, cerebellum, signal transduction
- MeSH terms
- Animals, Ataxia, Binding Sites, Brain, Carbachol, Cerebellum, Cycloleucine, Epilepsy, Hippocampus, Isoenzymes, Phosphatidylinositols, Type C Phospholipases, Piperazines, Receptors, Muscarinic, Signal Transduction, Mutagenesis, Serotonin Receptor Agonists, Receptors, Metabotropic Glutamate, Mice, Knockout, Muscarinic Agonists, Mice, Phospholipase C beta
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