2024
Compartment-specific regulation of NaV1.7 in sensory neurons after acute exposure to TNF-α
Tyagi S, Higerd-Rusli G, Ghovanloo M, Dib-Hajj F, Zhao P, Liu S, Kim D, Shim J, Park K, Waxman S, Choi J, Dib-Hajj S. Compartment-specific regulation of NaV1.7 in sensory neurons after acute exposure to TNF-α. Cell Reports 2024, 43: 113685. PMID: 38261513, PMCID: PMC10947185, DOI: 10.1016/j.celrep.2024.113685.Peer-Reviewed Original ResearchTNF-aSensory neuronsEffect of TNF-aSensory neuron excitabilityTumor necrosis factor-aRegulation of NaV1.7Voltage-gated sodiumPro-inflammatory cytokinesCompartment-specific effectsNeuronal plasma membraneSensitize nociceptorsNeuronal excitabilitySomatic membraneChannel N terminusElectrophysiological recordingsP38 MAPKIon channelsFactor AAcute exposureMolecular determinantsNeuronsAxonal endingsPhospho-acceptor sitesPlasma membraneCompartment-specific regulation
2023
Inflammation differentially controls transport of depolarizing Nav versus hyperpolarizing Kv channels to drive rat nociceptor activity
Higerd-Rusli G, Tyagi S, Baker C, Liu S, Dib-Hajj F, Dib-Hajj S, Waxman S. Inflammation differentially controls transport of depolarizing Nav versus hyperpolarizing Kv channels to drive rat nociceptor activity. Proceedings Of The National Academy Of Sciences Of The United States Of America 2023, 120: e2215417120. PMID: 36897973, PMCID: PMC10089179, DOI: 10.1073/pnas.2215417120.Peer-Reviewed Original ResearchConceptsCell biological mechanismsAxonal surfaceLive-cell imagingIon channel traffickingAnterograde transport vesiclesTransport vesiclesInflammatory mediatorsChannel traffickingPlasma membraneVesicular loadingIon channelsKv channelsPotential therapeutic targetPotassium channel KSodium channel NaTraffickingBiological mechanismsTherapeutic targetAbundanceRetrograde transportDistal axonsChannel NaInflammatory painNociceptor activityAxonal transport
2022
The fates of internalized NaV1.7 channels in sensory neurons: Retrograde cotransport with other ion channels, axon-specific recycling, and degradation
Higerd-Rusli G, Tyagi S, Liu S, Dib-Hajj F, Waxman S, Dib-Hajj S. The fates of internalized NaV1.7 channels in sensory neurons: Retrograde cotransport with other ion channels, axon-specific recycling, and degradation. Journal Of Biological Chemistry 2022, 299: 102816. PMID: 36539035, PMCID: PMC9843449, DOI: 10.1016/j.jbc.2022.102816.Peer-Reviewed Original ResearchConceptsMembrane proteinsIon channelsNeuronal functionDistinct neuronal compartmentsAxonal membrane proteinsRetrograde traffickingNeuronal polarityRecycling pathwayLate endosomesPlasma membraneSpecific proteinsAxonal traffickingNovel mechanismCell membraneSodium channel NaNeuronal compartmentsMultiple pathwaysLive neuronsVoltage-gated sodium channel NaProteinEndocytosisMembrane specializationsTraffickingMembraneChannel Na
2020
A 49-residue sequence motif in the C terminus of Nav1.9 regulates trafficking of the channel to the plasma membrane
Sizova D, Huang J, Akin E, Estacion M, Gomis-Perez C, Waxman S, Dib-Hajj S. A 49-residue sequence motif in the C terminus of Nav1.9 regulates trafficking of the channel to the plasma membrane. Journal Of Biological Chemistry 2020, 295: 1077-1090. DOI: 10.1016/s0021-9258(17)49917-0.Peer-Reviewed Original ResearchPlasma membraneC-terminusHEK293 cellsHigh-resolution live microscopyC-terminal motifHeterologous expression systemC-terminal chimerasHigh-throughput assaysSequence motifsCytoplasmic faceHeterologous systemsVoltage-gated sodium channel Nav1.9Live microscopyRecombinant expressionExpression systemLong motifsMechanistic basisFunctional expressionFunctional studiesTerminusLow functional expressionMotifChannel chimeraExpression levelsChimeras