Compartment-specific regulation of NaV1.7 in sensory neurons after acute exposure to TNF-α
Summary: 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 excitabili...
| Main Authors: | , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Elsevier
2024-02-01
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| Series: | Cell Reports |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S2211124724000135 |
| _version_ | 1797291806757486592 |
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| author | Sidharth Tyagi Grant P. Higerd-Rusli Mohammad-Reza Ghovanloo Fadia Dib-Hajj Peng Zhao Shujun Liu Dong-Hyun Kim Ji Seon Shim Kang-Sik Park Stephen G. Waxman Jin-Sung Choi Sulayman D. Dib-Hajj |
| author_facet | Sidharth Tyagi Grant P. Higerd-Rusli Mohammad-Reza Ghovanloo Fadia Dib-Hajj Peng Zhao Shujun Liu Dong-Hyun Kim Ji Seon Shim Kang-Sik Park Stephen G. Waxman Jin-Sung Choi Sulayman D. Dib-Hajj |
| author_sort | Sidharth Tyagi |
| collection | DOAJ |
| description | Summary: 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. |
| first_indexed | 2024-03-07T19:43:04Z |
| format | Article |
| id | doaj.art-fd5e2249aa9a4d75bd40c729fcbfa8f5 |
| institution | Directory Open Access Journal |
| issn | 2211-1247 |
| language | English |
| last_indexed | 2024-03-07T19:43:04Z |
| publishDate | 2024-02-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Cell Reports |
| spelling | doaj.art-fd5e2249aa9a4d75bd40c729fcbfa8f52024-02-29T05:18:35ZengElsevierCell Reports2211-12472024-02-01432113685Compartment-specific regulation of NaV1.7 in sensory neurons after acute exposure to TNF-αSidharth Tyagi0Grant P. Higerd-Rusli1Mohammad-Reza Ghovanloo2Fadia Dib-Hajj3Peng Zhao4Shujun Liu5Dong-Hyun Kim6Ji Seon Shim7Kang-Sik Park8Stephen G. Waxman9Jin-Sung Choi10Sulayman D. Dib-Hajj11Medical 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 Connecticut Healthcare System, West Haven, CT 06516, USA; Corresponding authorMedical 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 Connecticut Healthcare System, West Haven, CT 06516, USACenter 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, USACenter 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, USACenter 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, USACenter 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, USAIntegrated 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 KoreaDepartment of Physiology, Kyung Hee University School of Medicine, Seoul 02447, South KoreaDepartment of Physiology, Kyung Hee University School of Medicine, Seoul 02447, South KoreaCenter 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; Corresponding authorIntegrated Research Institute of Pharmaceutical Science, College of Pharmacy, The Catholic University of Korea, Bucheon 14662, South Korea; Corresponding authorCenter 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; Corresponding authorSummary: 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.http://www.sciencedirect.com/science/article/pii/S2211124724000135CP: Neuroscience |
| spellingShingle | Sidharth Tyagi Grant P. Higerd-Rusli Mohammad-Reza Ghovanloo Fadia Dib-Hajj Peng Zhao Shujun Liu Dong-Hyun Kim Ji Seon Shim Kang-Sik Park Stephen G. Waxman Jin-Sung Choi Sulayman D. Dib-Hajj Compartment-specific regulation of NaV1.7 in sensory neurons after acute exposure to TNF-α Cell Reports CP: Neuroscience |
| title | Compartment-specific regulation of NaV1.7 in sensory neurons after acute exposure to TNF-α |
| title_full | Compartment-specific regulation of NaV1.7 in sensory neurons after acute exposure to TNF-α |
| title_fullStr | Compartment-specific regulation of NaV1.7 in sensory neurons after acute exposure to TNF-α |
| title_full_unstemmed | Compartment-specific regulation of NaV1.7 in sensory neurons after acute exposure to TNF-α |
| title_short | Compartment-specific regulation of NaV1.7 in sensory neurons after acute exposure to TNF-α |
| title_sort | compartment specific regulation of nav1 7 in sensory neurons after acute exposure to tnf α |
| topic | CP: Neuroscience |
| url | http://www.sciencedirect.com/science/article/pii/S2211124724000135 |
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