title: Tetrodotoxin-resistant voltage-gated sodium channel Nav 1.8 constitutively interacts with ankyrin G.
abstract: The tetrodotoxin-resistant (TTX-R) voltage-gated sodium channel Nav 1.8 is predominantly expressed in peripheral afferent neurons, but in case of neuronal injury an ectopic and detrimental expression of Nav 1.8 occurs in neurons of the CNS. In CNS neurons, Nav 1.2 and Nav 1.6 channels accumulate at the axon initial segment, the site of the generation of the action potential, through a direct interaction with the scaffolding protein ankyrin G (ankG). This interaction is regulated by protein kinase CK2 phosphorylation. In this study, we quantitatively analyzed the interaction between Nav 1.8 and ankG. GST pull-down assay and surface plasmon resonance technology revealed that Nav 1.8 strongly and constitutively interacts with ankG, in comparison to what observed for Nav 1.2. An ion channel bearing the ankyrin-binding motif of Nav 1.8 displaced the endogenous Nav 1 accumulation at the axon initial segment of hippocampal neurons. Finally, Nav 1.8 and ankG co-localized in skin nerves fibers. Altogether, these results indicate that Nav 1.8 carries all the information required for its localization at ankG micro-domains. The constitutive binding of Nav 1.8 with ankG could contribute to the pathological aspects of illnesses where Nav 1.8 is ectopically expressed in CNS neurons.
authors.affiliation: Aix Marseille Université, CNRS, CRN2M-UMR7286, Marseille, France.
authors.forename: Audrey
authors.initials: A
authors.lastname: Montersino
authors.forename: Anna
authors.initials: A
authors.lastname: Brachet
authors.forename: Géraldine
authors.initials: G
authors.lastname: Ferracci
authors.forename: Marie-Pierre
authors.initials: MP
authors.lastname: Fache
authors.forename: Stephanie
authors.initials: S
authors.lastname: Angles d'Ortoli
authors.forename: Wenjing
authors.initials: W
authors.lastname: Liu
authors.forename: Fanny
authors.initials: F
authors.lastname: Rueda-Boroni
authors.forename: Francis
authors.initials: F
authors.lastname: Castets
authors.forename: Bénédicte
authors.initials: B
authors.lastname: Dargent
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D017487:Ankyrins / Q000378:metabolism*; D002478:Cells, Cultured; D005260:Female; D008297:Male; D051379:Mice; D008969:Molecular Sequence Data; D062559:NAV1.8 Voltage-Gated Sodium Channel / Q000378:metabolism*; D011247:Pregnancy; D011485:Protein Binding / Q000502:physiology; D051381:Rats; D017208:Rats, Wistar; D026941:Sodium Channel Blockers / Q000494:pharmacology*; D013779:Tetrodotoxin / Q000494:pharmacology*
chemical_list: C490614:Ank3 protein, rat; D017487:Ankyrins; D062559:NAV1.8 Voltage-Gated Sodium Channel; C568318:Scn10a protein, mouse; D026941:Sodium Channel Blockers; D013779:Tetrodotoxin
keywords: TTX-R voltage gated sodium channels; ankyrins; axon initial segment