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Mapping protein interactions of sodium channel NaV1.7 using epitope-tagged gene-targeted mice.
Kanellopoulos, Alexandros H; Koenig, Jennifer; Huang, Honglei; Pyrski, Martina; Millet, Queensta; Lolignier, Stéphane; Morohashi, Toru; Gossage, Samuel J; Jay, Maude; Linley, John E; Baskozos, Georgios; Kessler, Benedikt M; Cox, James J; Dolphin, Annette C; Zufall, Frank; Wood, John N; Zhao, Jing.
  • Kanellopoulos AH; Molecular Nociception Group, WIBR, University College London, London, UK.
  • Koenig J; Molecular Nociception Group, WIBR, University College London, London, UK.
  • Huang H; TDI Mass Spectrometry Laboratory, Target Discovery Institute, University of Oxford, Oxford, UK.
  • Pyrski M; Center for Integrative Physiology and Molecular Medicine, Saarland University, Homburg, Germany.
  • Millet Q; Molecular Nociception Group, WIBR, University College London, London, UK.
  • Lolignier S; Molecular Nociception Group, WIBR, University College London, London, UK.
  • Morohashi T; Université Clermont Auvergne, Inserm U1107 Neuro-Dol, Pharmacologie Fondamentale et Clinique de la Douleur, Clermont-Ferrand, France.
  • Gossage SJ; Molecular Nociception Group, WIBR, University College London, London, UK.
  • Jay M; Molecular Nociception Group, WIBR, University College London, London, UK.
  • Linley JE; Molecular Nociception Group, WIBR, University College London, London, UK.
  • Baskozos G; Molecular Nociception Group, WIBR, University College London, London, UK.
  • Kessler BM; Neuroscience, IMED Biotech Unit, AstraZeneca, Cambridge, UK.
  • Cox JJ; Division of Bioscience, University College London, London, UK.
  • Dolphin AC; TDI Mass Spectrometry Laboratory, Target Discovery Institute, University of Oxford, Oxford, UK.
  • Zufall F; Molecular Nociception Group, WIBR, University College London, London, UK.
  • Wood JN; Department of Neuroscience, Physiology and Pharmacology, University College London, London, UK.
  • Zhao J; Center for Integrative Physiology and Molecular Medicine, Saarland University, Homburg, Germany.
EMBO J ; 37(3): 427-445, 2018 02 01.
Article en En | MEDLINE | ID: mdl-29335280
The voltage-gated sodium channel NaV1.7 plays a critical role in pain pathways. We generated an epitope-tagged NaV1.7 mouse that showed normal pain behaviours to identify channel-interacting proteins. Analysis of NaV1.7 complexes affinity-purified under native conditions by mass spectrometry revealed 267 proteins associated with Nav1.7 in vivo The sodium channel ß3 (Scn3b), rather than the ß1 subunit, complexes with Nav1.7, and we demonstrate an interaction between collapsing-response mediator protein (Crmp2) and Nav1.7, through which the analgesic drug lacosamide regulates Nav1.7 current density. Novel NaV1.7 protein interactors including membrane-trafficking protein synaptotagmin-2 (Syt2), L-type amino acid transporter 1 (Lat1) and transmembrane P24-trafficking protein 10 (Tmed10) together with Scn3b and Crmp2 were validated by co-immunoprecipitation (Co-IP) from sensory neuron extract. Nav1.7, known to regulate opioid receptor efficacy, interacts with the G protein-regulated inducer of neurite outgrowth (Gprin1), an opioid receptor-binding protein, demonstrating a physical and functional link between Nav1.7 and opioid signalling. Further information on physiological interactions provided with this normal epitope-tagged mouse should provide useful insights into the many functions now associated with the NaV1.7 channel.
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Texto completo: 1 Banco de datos: MEDLINE Asunto principal: Dolor / Células Receptoras Sensoriales / Receptores de N-Metil-D-Aspartato / Receptores Opioides / Canal de Sodio Activado por Voltaje NAV1.7 / Proteínas del Tejido Nervioso Tipo de estudio: Prognostic_studies Límite: Animals / Humans Idioma: En Año: 2018 Tipo del documento: Article
Texto completo
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Texto completo: 1 Banco de datos: MEDLINE Asunto principal: Dolor / Células Receptoras Sensoriales / Receptores de N-Metil-D-Aspartato / Receptores Opioides / Canal de Sodio Activado por Voltaje NAV1.7 / Proteínas del Tejido Nervioso Tipo de estudio: Prognostic_studies Límite: Animals / Humans Idioma: En Año: 2018 Tipo del documento: Article