Kanellopoulos, A, Koenig, J, Huang, H, Pyrski, M, Millet, Q, Lolignier, S, Morohashi, T, Gossage, S, Jay, M, Linley, J, Baskozos, G, Kessler, B, Cox, J, Dolphin, A, Zufall, F, Wood, J, Zhao, J, Wolfson Institute for Biomedical Research (WIBR), University College of London [London] (UCL), Target Discovery Institute [Oxford, UK] (TDI), University of Oxford, and Saarland University [Saarbrücken]
International audience; The voltage-gated sodium channel Na V 1.7 plays a critical role in pain pathways. We generated an epitope-tagged Na V 1.7 mouse that showed normal pain behaviours to identify channel-interacting proteins. Analysis of Na V 1.7 complexes affinity-purified under native conditions by mass spectrometry revealed 267 proteins associated with Nav1.7 in vivo. The sodium channel b3 (Scn3b), rather than the b1 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 Na V 1.7 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 Na V 1.7 channel.