ArticleProceedings of the National Academy of Sciences of the United States of America2011
Palmitoylation influences the function and pharmacology of sodium channels.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 29 papers.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Who cites it
29 citing papers in PubMed, 39 citations in OpenAlex.
- Cytoskeletal scaffolding of NaCurrent opinion in cell biology · 2025Review
- Phrixotoxin-3 binds to three distinct antagonistic sites on human NaCell research · 2025Article
- Mechanisms and functions of protein S-acylation.Nature reviews. Molecular cell biology · 2024Review
- Regulating neuronal excitability: The role ofPNAS nexus · 2024Article
- Review
- Palmitoylation of Voltage-Gated Ion Channels.International journal of molecular sciences · 2022Review
- A sticky situation: regulation and function of protein palmitoylation with a spotlight on the axon and axon initial segment.Neuronal signaling · 2021Review
- Functional cross-talk between phosphorylation and disease-causing mutations in the cardiac sodium channel NaProceedings of the National Academy of Sciences of the United States of America · 2021Article
- Cutting out the fat: Site-specific deacylation of an ion channel.The Journal of biological chemistry · 2020Article
- Spider venom-derived peptide induces hyperalgesia in NaNature communications · 2020Article
- Article
- Spider Knottin Pharmacology at Voltage-Gated Sodium Channels and Their Potential to Modulate Pain Pathways.Toxins · 2019Review
- Selective NaProceedings of the National Academy of Sciences of the United States of America · 2018Article
- The NaFrontiers in pharmacology · 2018Review
- Post-translational palmitoylation controls the voltage gating and lipid raft association of the CALHM1 channel.The Journal of physiology · 2017Article
- Regulation of TRPP3 Channel Function by N-terminal Domain Palmitoylation and Phosphorylation.The Journal of biological chemistry · 2016Article
- Cardiac sodium channel palmitoylation regulates channel availability and myocyte excitability with implications for arrhythmia generation.Nature communications · 2016Article
- Molecular Interactions between Tarantula Toxins and Low-Voltage-Activated Calcium Channels.Scientific reports · 2016Article
- An update on transcriptional and post-translational regulation of brain voltage-gated sodium channels.Amino acids · 2016Review
- Human CLC-K Channels Require Palmitoylation of Their Accessory Subunit Barttin to Be Functional.The Journal of biological chemistry · 2015Article
Corrections and comments
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Authors and funding
3 authors at 2 institutions in 1 country.
Funding
Abstract
Palmitoylation is a common lipid modification known to regulate the functional properties of various proteins and is a vital step in the biosynthesis of voltage-activated sodium (Nav) channels. We discovered a mutation in an intracellular loop of rNav1.2a (G1079C), which results in a higher apparent affinity for externally applied PaurTx3 and ProTx-II, two voltage sensor toxins isolated from tarantula venom. To explore whether palmitoylation of the introduced cysteine underlies this observation, we compared channel susceptibility to a range of animal toxins in the absence and presence of 2-Br-palmitate, a palmitate analog that prevents palmitate incorporation into proteins, and found that palmitoylation contributes to the increased affinity of PaurTx3 and ProTx-II for G1079C. Further investigations with 2-Br-palmitate revealed that palmitoylation can regulate the gating and pharmacology of wild-type (wt) rNav1.2a. To identify rNav1.2a palmitoylation sites contributing to these phenomena, we substituted three endogenous cysteines predicted to be palmitoylated and found that the gating behavior of this triple cysteine mutant is similar to wt rNav1.2a treated with 2-Br-palmitate. As with chemically depalmitoylated rNav1.2a channels, this mutant also exhibits an increased susceptibility for PaurTx3. Additional mutagenesis experiments showed that palmitoylation of one cysteine in particular (C1182) primarily influences PaurTx3 sensitivity and may enhance the inactivation process of wt rNav1.2a. Overall, our results demonstrate that lipid modifications are capable of altering the gating and pharmacological properties of rNav1.2a.
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Registered trials
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.