UCL Discovery
UCL home » Library Services » Electronic resources » UCL Discovery

Mapping protein interactions of sodium channel NaV1.7 using epitope-tagged gene targeted mice

Kanellopoulos, AH; Koenig, J; Huang, H; Pyrski, M; Millet, Q; Lolignier, S; Morohashi, T; ... Zhao, J; + view all (2018) Mapping protein interactions of sodium channel NaV1.7 using epitope-tagged gene targeted mice. The EMBO Journal , 37 (3) pp. 427-445. 10.15252/embj.201796692. Green open access

[img]
Preview
Text
Zhao_427.full.pdf - Published version

Download (1MB) | Preview

Abstract

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 β3 (Scn3b), rather than the β1 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.

Type: Article
Title: Mapping protein interactions of sodium channel NaV1.7 using epitope-tagged gene targeted mice
Open access status: An open access version is available from UCL Discovery
DOI: 10.15252/embj.201796692
Publisher version: http://doi.org/10.15252/embj.201796692
Language: English
Additional information: © 2018 The Authors. Published under the terms of the CC BY 4.0 license
Keywords: NaV1.7; pain; protein–protein interactor; sensory neuron; sodium channel
UCL classification: UCL
UCL > Provost and Vice Provost Offices
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences > Div of Biosciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences > Div of Biosciences > Neuro, Physiology and Pharmacology
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Div of Medicine
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Div of Medicine > Wolfson Inst for Biomedical Research
URI: https://discovery.ucl.ac.uk/id/eprint/10040485
Downloads since deposit
129Downloads
Download activity - last month
Download activity - last 12 months
Downloads by country - last 12 months

Archive Staff Only

View Item View Item