ArticleThe Journal of biological chemistry2014
A mechanism regulating G protein-coupled receptor signaling that requires cycles of protein palmitoylation and depalmitoylation.
Article in The Journal of biological chemistry, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 23 papers.
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Who cites it
23 citing papers in PubMed, 44 citations in OpenAlex.
- ProteinJournal of pharmaceutical analysis · 2026Review
- S-Palmitoylation of Synaptic Proteins in Neuronal Plasticity in Normal and Pathological Brains.Cells · 2023Review
- Palmitoylation of Voltage-Gated Ion Channels.International journal of molecular sciences · 2022Review
- Mechanisms and Regulation of Neuronal GABACurrent topics in behavioral neurosciences · 2022Review
- Article
- ABHD17 regulation of plasma membrane palmitoylation and N-Ras-dependent cancer growth.Nature chemical biology · 2021Article
- Control of protein palmitoylation by regulating substrate recruitment to a zDHHC-protein acyltransferase.Communications biology · 2020Article
- Lipid Modifications in Cilia Biology.Journal of clinical medicine · 2019Review
- Lipopolysaccharide Upregulates Palmitoylated Enzymes of the Phosphatidylinositol Cycle: An Insight from Proteomic Studies.Molecular & cellular proteomics : MCP · 2018Article
- Protein depalmitoylases.Critical reviews in biochemistry and molecular biology · 2018Review
- Regulation of neurite morphogenesis by interaction between R7 regulator of G protein signaling complexes and G protein subunit GαThe Journal of biological chemistry · 2017Article
- Protein palmitoylation: Palmitoyltransferases and their specificity.Experimental biology and medicine (Maywood, N.J.) · 2017Article
- Protein Palmitoylation and Its Role in Bacterial and Viral Infections.Frontiers in immunology · 2017Review
- Roles for Regulator of G Protein Signaling Proteins in Synaptic Signaling and Plasticity.Molecular pharmacology · 2016Review
- Metabolomics Reveals New Mechanisms for Pathogenesis in Barth Syndrome and Introduces Novel Roles for Cardiolipin in Cellular Function.PloS one · 2016Article
- Article
- New paradigms in GPCR drug discovery.Biochemical pharmacology · 2015Review
- The physiology of protein S-acylation.Physiological reviews · 2015Review
- Systematic siRNA Screen Unmasks NSCLC Growth Dependence by Palmitoyltransferase DHHC5.Molecular cancer research : MCR · 2015Article
- Exosomal sorting of the viral oncoprotein LMP1 is restrained by TRAF2 association at signalling endosomes.Journal of extracellular vesicles · 2015Article
Corrections and comments
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Authors and funding
9 authors at 2 institutions in 1 country.
Funding
Abstract
Reversible attachment and removal of palmitate or other long-chain fatty acids on proteins has been hypothesized, like phosphorylation, to control diverse biological processes. Indeed, palmitate turnover regulates Ras trafficking and signaling. Beyond this example, however, the functions of palmitate turnover on specific proteins remain poorly understood. Here, we show that a mechanism regulating G protein-coupled receptor signaling in neuronal cells requires palmitate turnover. We used hexadecyl fluorophosphonate or palmostatin B to inhibit enzymes in the serine hydrolase family that depalmitoylate proteins, and we studied R7 regulator of G protein signaling (RGS)-binding protein (R7BP), a palmitoylated allosteric modulator of R7 RGS proteins that accelerate deactivation of Gi/o class G proteins. Depalmitoylation inhibition caused R7BP to redistribute from the plasma membrane to endomembrane compartments, dissociated R7BP-bound R7 RGS complexes from Gi/o-gated G protein-regulated inwardly rectifying K(+) (GIRK) channels and delayed GIRK channel closure. In contrast, targeting R7BP to the plasma membrane with a polybasic domain and an irreversibly attached lipid instead of palmitate rendered GIRK channel closure insensitive to depalmitoylation inhibitors. Palmitate turnover therefore is required for localizing R7BP to the plasma membrane and facilitating Gi/o deactivation by R7 RGS proteins on GIRK channels. Our findings broaden the scope of biological processes regulated by palmitate turnover on specific target proteins. Inhibiting R7BP depalmitoylation may provide a means of enhancing GIRK activity in neurological disorders.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.