ArticleCNS & neurological disorders drug targets2014
Modulation of the FGF14:FGF14 homodimer interaction through short peptide fragments.
Article in CNS & neurological disorders drug targets, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers.
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Who cites it
18 citing papers in PubMed, 19 citations in OpenAlex.
- Genome-Wide Analysis of lncRNA and mRNA Expression in the Uterus of Laying Hens during Aging.Genes · 2023Article
- Glycogen Synthase Kinase 3: Ion Channels, Plasticity, and Diseases.International journal of molecular sciences · 2022Review
- Differential Modulation of the Voltage-Gated NaFrontiers in molecular biosciences · 2021Article
- Development of Allosteric Modulators of Voltage-Gated NaCurrent topics in medicinal chemistry · 2021Review
- 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
- Effects of FGF14 and NaThe Journal of general physiology · 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
- Functional Modulation of Voltage-Gated Sodium Channels by a FGF14-Based Peptidomimetic.ACS chemical neuroscience · 2018Article
- PPARgamma agonists rescue increased phosphorylation of FGF14 at S226 in the Tg2576 mouse model of Alzheimer's disease.Experimental neurology · 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
- 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
- Identification of Amino Acid Residues in Fibroblast Growth Factor 14 (FGF14) Required for Structure-Function Interactions with Voltage-gated Sodium Channel Nav1.6.The Journal of biological chemistry · 2016Article
- Parallel fiber to Purkinje cell synaptic impairment in a mouse model of spinocerebellar ataxia type 27.Frontiers in cellular neuroscience · 2015Article
- The Fibroblast Growth Factor signaling pathway.Wiley interdisciplinary reviews. Developmental biologyReview
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Authors and funding
5 authors at 1 institution in 1 country.
Funding
Abstract
Fibroblast growth factor 14 (FGF14) is a member of the intracellular FGF (iFGFs) family and a functionally relevant component of the neuronal voltage-gated Na(+) (Nav) channel complex. Through a monomeric interaction with the intracellular C-terminus of neuronal Nav channels, FGF14 modulates Na(+) currents in an Nav isoform-specific manner serving as a fine-tuning regulator of excitability. Previous studies based on the highly homologous FGF13 homodimer crystal structure have proposed a conserved protein:protein interaction (PPI) interface common to both Nav channel binding and iFGF homodimer formation. This interface could provide a novel target for drug design against neuronal Nav channels. Here, we provide the first in-cell reconstitution of the FGF14:FGF14 protein complex and measure the dimer interaction using the split-luciferase complementation assay (LCA). Based on the FGF14 dimer structure generated in silico, we designed short peptide fragments against the FGF14 dimer interface. One of these fragments, FLPK aligns with the pocket defined by the β12-strand and β8-β9 loop, reducing the FGF14:FGF14 dimer interaction by 25% as measured by LCA. We further compared the relative interaction strength of FGF14 wild type homodimers with FGF14 hetero- and homodimers carrying double N mutations at the Y153 and V155 residues, located at the β8-β9 loop. The Y153N/V155N double mutation counteracts the FLPK effect by increasing the strength of the dimer interaction. These data suggest that the β12 strand of FGF14 might serve as scaffold for drug design against neuronal FGF14 dimers and Nav channels.
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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.