Mapping Protein Interactions of Sodium Channel Na1.7 Using Epitope-tagged Gene-targeted Mice

Overview

Journal EMBO J

Specialties Biotechnology
Molecular Biology

Date 2018 Jan 17

PMID 29335280

Citations 33

Authors

Alexandros H Kanellopoulos

Jennifer Koenig

Honglei Huang

Martina Pyrski

Queensta Millet

Stephane Lolignier

Toru Morohashi

Samuel J Gossage

Maude Jay

John E Linley

Georgios Baskozos

Benedikt M Kessler

James J Cox

Annette C Dolphin

Frank Zufall

John N Wood

Jing Zhao

Affiliations

Soon will be listed here.

Abstract

The voltage-gated sodium channel Na1.7 plays a critical role in pain pathways. We generated an epitope-tagged Na1.7 mouse that showed normal pain behaviours to identify channel-interacting proteins. Analysis of Na1.7 complexes affinity-purified under native conditions by mass spectrometry revealed 267 proteins associated with Nav1.7 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 Na1.7 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 Na1.7 channel.

Citing Articles

Sodium channels Na1.7, Na1.8 and pain; two distinct mechanisms for Na1.7 null analgesia.

Iseppon F, Kanellopoulos A, Tian N, Zhou J, Caan G, Chiozzi R Neurobiol Pain. 2024; 16:100168.

PMID: 39559752 PMC: 11570969. DOI: 10.1016/j.ynpai.2024.100168.

[Additional experience with medicinal treatment of trigeminal nerve pain].

Liedtke W Schmerz. 2024; 38(5):359-361.

PMID: 39141098 DOI: 10.1007/s00482-024-00820-2.

Persistent sodium currents in neurons: potential mechanisms and pharmacological blockers.

Muller P, Draguhn A, Egorov A Pflugers Arch. 2024; 476(10):1445-1473.

PMID: 38967655 PMC: 11381486. DOI: 10.1007/s00424-024-02980-7.

The pain target Na1.7 is expressed late during human iPS cell differentiation into sensory neurons as determined in high-resolution imaging.

Liu Y, Balaji R, Szymanski de Toledo M, Ernst S, Hautvast P, Kesdogan A Pflugers Arch. 2024; 476(6):975-992.

PMID: 38538988 PMC: 11139713. DOI: 10.1007/s00424-024-02945-w.

Anxiety and dysautonomia symptoms in patients with a Na1.7 mutation and the potential benefits of low-dose short-acting guanfacine.

de Cassia Collaco R, Lammens M, Blevins C, Rodgers K, Gurau A, Yamauchi S Clin Auton Res. 2023; 34(1):191-201.

PMID: 38064009 PMC: 11805752. DOI: 10.1007/s10286-023-01004-1.

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