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Compartment-specific regulation of NaV1.7 in sensory neurons after acute exposure to TNF-α.
Tyagi, Sidharth; Higerd-Rusli, Grant P; Ghovanloo, Mohammad-Reza; Dib-Hajj, Fadia; Zhao, Peng; Liu, Shujun; Kim, Dong-Hyun; Shim, Ji Seon; Park, Kang-Sik; Waxman, Stephen G; Choi, Jin-Sung; Dib-Hajj, Sulayman D.
Afiliação
  • Tyagi S; Medical Scientist Training Program, Yale School of Medicine, New Haven, CT 06511, USA; Center for Neuroscience and Regeneration Research, West Haven, CT 06516, USA; Department of Neurology, Yale School of Medicine, New Haven, CT 06516, USA; Center for Restoration of Nervous System Function, VA Conne
  • Higerd-Rusli GP; Medical Scientist Training Program, Yale School of Medicine, New Haven, CT 06511, USA; Center for Neuroscience and Regeneration Research, West Haven, CT 06516, USA; Department of Neurology, Yale School of Medicine, New Haven, CT 06516, USA; Center for Restoration of Nervous System Function, VA Conne
  • Ghovanloo MR; Center for Neuroscience and Regeneration Research, West Haven, CT 06516, USA; Department of Neurology, Yale School of Medicine, New Haven, CT 06516, USA; Center for Restoration of Nervous System Function, VA Connecticut Healthcare System, West Haven, CT 06516, USA.
  • Dib-Hajj F; Center for Neuroscience and Regeneration Research, West Haven, CT 06516, USA; Department of Neurology, Yale School of Medicine, New Haven, CT 06516, USA; Center for Restoration of Nervous System Function, VA Connecticut Healthcare System, West Haven, CT 06516, USA.
  • Zhao P; Center for Neuroscience and Regeneration Research, West Haven, CT 06516, USA; Department of Neurology, Yale School of Medicine, New Haven, CT 06516, USA; Center for Restoration of Nervous System Function, VA Connecticut Healthcare System, West Haven, CT 06516, USA.
  • Liu S; Center for Neuroscience and Regeneration Research, West Haven, CT 06516, USA; Department of Neurology, Yale School of Medicine, New Haven, CT 06516, USA; Center for Restoration of Nervous System Function, VA Connecticut Healthcare System, West Haven, CT 06516, USA.
  • Kim DH; Integrated Research Institute of Pharmaceutical Science, College of Pharmacy, The Catholic University of Korea, Bucheon 14662, South Korea; New Drug Development Center, Daegu-Gyeongbuk Medical Innovation Foundation (DGMIF), Daegu 41061, South Korea.
  • Shim JS; Department of Physiology, Kyung Hee University School of Medicine, Seoul 02447, South Korea.
  • Park KS; Department of Physiology, Kyung Hee University School of Medicine, Seoul 02447, South Korea.
  • Waxman SG; Center for Neuroscience and Regeneration Research, West Haven, CT 06516, USA; Department of Neurology, Yale School of Medicine, New Haven, CT 06516, USA; Center for Restoration of Nervous System Function, VA Connecticut Healthcare System, West Haven, CT 06516, USA. Electronic address: stephen.waxman
  • Choi JS; Integrated Research Institute of Pharmaceutical Science, College of Pharmacy, The Catholic University of Korea, Bucheon 14662, South Korea. Electronic address: jinsung.choi@catholic.ac.kr.
  • Dib-Hajj SD; Center for Neuroscience and Regeneration Research, West Haven, CT 06516, USA; Department of Neurology, Yale School of Medicine, New Haven, CT 06516, USA; Center for Restoration of Nervous System Function, VA Connecticut Healthcare System, West Haven, CT 06516, USA. Electronic address: sulayman.dib-h
Cell Rep ; 43(2): 113685, 2024 Feb 27.
Article em En | MEDLINE | ID: mdl-38261513
ABSTRACT
Tumor necrosis factor α (TNF-α) is a major pro-inflammatory cytokine, important in many diseases, that sensitizes nociceptors through its action on a variety of ion channels, including voltage-gated sodium (NaV) channels. We show here that TNF-α acutely upregulates sensory neuron excitability and current density of threshold channel NaV1.7. Using electrophysiological recordings and live imaging, we demonstrate that this effect on NaV1.7 is mediated by p38 MAPK and identify serine 110 in the channel's N terminus as the phospho-acceptor site, which triggers NaV1.7 channel insertion into the somatic membrane. We also show that the N terminus of NaV1.7 is sufficient to mediate this effect. Although acute TNF-α treatment increases NaV1.7-carrying vesicle accumulation at axonal endings, we did not observe increased channel insertion into the axonal membrane. These results identify molecular determinants of TNF-α-mediated regulation of NaV1.7 in sensory neurons and demonstrate compartment-specific effects of TNF-α on channel insertion in the neuronal plasma membrane.
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Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Células Receptoras Sensoriais / Fator de Necrose Tumoral alfa Tipo de estudo: Prognostic_studies Idioma: En Revista: Cell Rep Ano de publicação: 2024 Tipo de documento: Article

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Células Receptoras Sensoriais / Fator de Necrose Tumoral alfa Tipo de estudo: Prognostic_studies Idioma: En Revista: Cell Rep Ano de publicação: 2024 Tipo de documento: Article