ArticleAssay and drug development technologies2012
Bioluminescence methodology for the detection of protein-protein interactions within the voltage-gated sodium channel macromolecular complex.
Article in Assay and drug development technologies, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 32 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
32 citing papers in PubMed, 39 citations in OpenAlex.
- TNFR1 signaling converging on FGF14 controls neuronal hyperactivity and sickness behavior in experimental cerebral malaria.Journal of neuroinflammation · 2023Article
- Glycogen Synthase Kinase 3: Ion Channels, Plasticity, and Diseases.International journal of molecular sciences · 2022Review
- Article
- Inhibition of AKT Signaling Alters βIV Spectrin Distribution at the AIS and Increases Neuronal Excitability.Frontiers in molecular neuroscience · 2021Article
- Differential Modulation of the Voltage-Gated NaFrontiers in molecular biosciences · 2021Article
- Design, Synthesis, and Pharmacological Evaluation of Analogues Derived from the PLEV Tetrapeptide as Protein-Protein Interaction Modulators of Voltage-Gated Sodium Channel 1.6.Journal of medicinal chemistry · 2020Article
- JAK2 regulates Nav1.6 channel function via FGF14Biochimica et biophysica acta. Molecular cell research · 2020Article
- Bidirectional Modulation of the Voltage-Gated Sodium (Nav1.6) Channel by Rationally Designed Peptidomimetics.Molecules (Basel, Switzerland) · 2020Article
- Mapping of the FGF14:Nav1.6 complex interface reveals FLPK as a functionally active peptide modulating excitability.Physiological reports · 2020Article
- High-throughput screening against protein:protein interaction interfaces reveals anti-cancer therapeutics as potent modulators of the voltage-gated NaScientific reports · 2019Article
- Identification of peptidomimetics as novel chemical probes modulating fibroblast growth factor 14 (FGF14) and voltage-gated sodium channel 1.6 (Nav1.6) protein-protein interactions.Bioorganic & medicinal chemistry letters · 2019Article
- Voltage-gated sodium currents in cerebellar Purkinje neurons: functional and molecular diversity.Cellular and molecular life sciences : CMLS · 2018Review
- Functional Modulation of Voltage-Gated Sodium Channels by a FGF14-Based Peptidomimetic.ACS chemical neuroscience · 2018Article
- Article
- PPARgamma agonists rescue increased phosphorylation of FGF14 at S226 in the Tg2576 mouse model of Alzheimer's disease.Experimental neurology · 2017Article
- Decoy peptide targeted to Toll-IL-1R domain inhibits LPS and TLR4-active metabolite morphine-3 glucuronide sensitization of sensory neurons.Scientific reports · 2017Article
- Conditional knockout of Fgf13 in murine hearts increases arrhythmia susceptibility and reveals novel ion channel modulatory roles.Journal of molecular and cellular cardiology · 2017Article
- Intracellular Fibroblast Growth Factor 14: Emerging Risk Factor for Brain Disorders.Frontiers in cellular neuroscience · 2017Review
- Fibroblast Growth Factor 14 Modulates the Neurogenesis of Granule Neurons in the Adult Dentate Gyrus.Molecular neurobiology · 2016Article
- CK2 activity is required for the interaction of FGF14 with voltage-gated sodium channels and neuronal excitability.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2016Article
Corrections and comments
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Authors and funding
7 authors at 2 institutions in 1 country.
Funding
Abstract
Protein-protein interactions are critical molecular determinants of ion channel function and emerging targets for pharmacological interventions. Yet, current methodologies for the rapid detection of ion channel macromolecular complexes are still lacking. In this study we have adapted a split-luciferase complementation assay (LCA) for detecting the assembly of the voltage-gated Na+ (Nav) channel C-tail and the intracellular fibroblast growth factor 14 (FGF14), a functionally relevant component of the Nav channelosome that controls gating and targeting of Nav channels through direct interaction with the channel C-tail. In the LCA, two complementary N-terminus and C-terminus fragments of the firefly luciferase were fused, respectively, to a chimera of the CD4 transmembrane segment and the C-tail of Nav1.6 channel (CD4-Nav1.6-NLuc) or FGF14 (CLuc-FGF14). Co-expression of CLuc-FGF14 and CD4-Nav1.6-NLuc in live cells led to a robust assembly of the FGF14:Nav1.6 C-tail complex, which was attenuated by introducing single-point mutations at the predicted FGF14:Nav channel interface. To evaluate the dynamic regulation of the FGF14:Nav1.6 C-tail complex by signaling pathways, we investigated the effect of kinase inhibitors on the complex formation. Through a platform of counter screenings, we show that the p38/MAPK inhibitor, PD169316, and the IκB kinase inhibitor, BAY 11-7082, reduce the FGF14:Nav1.6 C-tail complementation, highlighting a potential role of the p38MAPK and the IκB/NFκB pathways in controlling neuronal excitability through protein-protein interactions. We envision the methodology presented here as a new valuable tool to allow functional evaluations of protein-channel complexes toward probe development and drug discovery targeting ion channels implicated in human disorders.
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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.