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Annexin II light chain regulates sensory neuron-specific sodium channel expression

Abstract

The tetrodotoxin-resistant sodium channel NaV1.8/SNS is expressed exclusively in sensory neurons and appears to have an important role in pain pathways1,2. Unlike other sodium channels, NaV1.8 is poorly expressed in cell lines even in the presence of accessory β-subunits3. Here we identify annexin II light chain4,5 (p11) as a regulatory factor that facilitates the expression of NaV1.8. p11 binds directly to the amino terminus of NaV1.8 and promotes the translocation of NaV1.8 to the plasma membrane, producing functional channels. The endogenous NaV1.8 current in sensory neurons is inhibited by antisense downregulation of p11 expression. Because direct association with p11 is required for functional expression of NaV1.8, disrupting this interaction may be a useful new approach to downregulating NaV1.8 and effecting analgesia6.

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Figure 1: p11 mRNA is expressed in DRG neurons and is upregulated by NGF.
Figure 2: p11 regulates trafficking of NaV1.8 from cytosol to plasma membrane.
Figure 3: p11 is required for expression of TTX-resistant inward currents in CHO-SNS22 and DRG neurons.

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Acknowledgements

We thank the MRC, the Wellcome Trust and the NIH (grants supporting M.C. and H.K.) for their generous support. We thank Stephen E. Moss and A. Schmidt for helpful advice.

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Correspondence to John N. Wood.

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Okuse, K., Malik-Hall, M., Baker, M. et al. Annexin II light chain regulates sensory neuron-specific sodium channel expression. Nature 417, 653–656 (2002). https://doi.org/10.1038/nature00781

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