RT Journal Article SR Electronic T1 Mapping protein interactions of sodium channel NaV1.7 using epitope-tagged gene targeted mice JF bioRxiv FD Cold Spring Harbor Laboratory SP 118497 DO 10.1101/118497 A1 Alexandros H. Kanellopoulos A1 Jennifer Koenig A1 Honglei Huang A1 Martina Pyrski A1 Queensta Millet A1 Stephane Lolignier A1 Toru Morohashi A1 Samuel J. Gossage A1 Maude Jay A1 John Linley A1 Georgios Baskozos A1 Benedikt Kessler A1 James J. Cox A1 Frank Zufall A1 John N. Wood A1 Jing Zhao YR 2017 UL http://biorxiv.org/content/early/2017/03/20/118497.abstract AB The voltage-gated sodium channel NaV1.7 plays a critical role in pain pathways. Besides action potential propagation, NaV1.7 regulates neurotransmitter release, integrates depolarizing inputs over long periods and regulates transcription. In order to better understand these functions, we generated an epitope-tagged NaV1.7 mouse that showed normal pain behavior. Analysis of NaV1.7 complexes affinity-purified under native conditions by mass spectrometry revealed 267 NaV1.7 associated proteins including known interactors, such as the sodium channel β3 subunit (Scn3b) and collapsin response mediator protein (Crmp2), and novel interactors. Selected novel NaV1.7 protein interactors membrane-trafficking protein synapototagmin-2 (Syt2), G protein-regulated inducer of neurite outgrowth 1 (Gprin1), L-type amino acid transporter 1 (Lat1) and transmembrane P24 trafficking protein 10 (Tmed10) together with Scn3b and Crmp2 were validated using co-immunoprecipitation and functional assays. The information provided with this physiologically normal epitope-tagged mouse should provide useful insights into the pain mechanisms associated with NaV1.7 channel function.