Tetrodotoxin-resistant voltage-gated sodium channel Nav 1.8 constitutively interacts with ankyrin G.

Audrey Montersino, Anna Brachet, Géraldine Ferracci, Marie-Pierre Fache, Stephanie Angles d'Ortoli, Wenjing Liu, Fanny Rueda-Boroni, Francis Castets, Bénédicte Dargent
J. Neurochem.. 2014-06-27; 131(1): 33-41
DOI: 10.1111/jnc.12785

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1. J Neurochem. 2014 Oct;131(1):33-41. doi: 10.1111/jnc.12785. Epub 2014 Jun 27.

Tetrodotoxin-resistant voltage-gated sodium channel Nav 1.8 constitutively
interacts with ankyrin G.

Montersino A(1), Brachet A, Ferracci G, Fache MP, Angles d’Ortoli S, Liu W,
Rueda-Boroni F, Castets F, Dargent B.

Author information:
(1)Aix Marseille Université, CNRS, CRN2M-UMR7286, Marseille, France.

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.

© 2014 International Society for Neurochemistry.

DOI: 10.1111/jnc.12785
PMID: 24903831 [Indexed for MEDLINE]

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