Na+ channels get anchored...with a little help

Abstract

Neurons have high densities of voltage-gated Na(+) channels that are restricted to axon initial segments and nodes of Ranvier, where they are responsible for initiating and propagating action potentials. New findings (Bréchet, A., M.-P. Fache, A. Brachet, G. Ferracci, A. Baude, M. Irondelle, S. Pereira, C. Leterrier, and B. Dargent. 2008. J. Cell Biol. 183:1101-1114) reveal that phosphorylation of several key serine residues by the protein kinase CK2 regulates Na(+) channel interactions with ankyrin G. The presence of CK2 at the axon initial segment and nodes of Ranvier provides a mechanism to regulate the specific accumulation and retention of Na(+) channels within these important domains.

Figure 1.

Spatially restricted CK2 activity increases the affinity of Na_v channels for ankG. (A) AISs have high densities of Na_v channels (red) and ankG (green). (A, inset) Nodes of Ranvier have complementary distributions of ankyrins, with ankB at paranodes (red) and ankG at nodes (green). Bars, 5 μm. (B) CK2 is restricted to the AIS and nodes of Ranvier, where it promotes the interaction between Na_v channels and ankG. AnkG also interacts with neurofascin-186 (NF-186) in a phosphorylation-dependent manner, and is linked to the cytoskeleton through βIV spectrin. In contrast, distal axons and paranodes contain ankB that is linked to the cytoskeleton through βII spectrin. CK2 is not present in these regions, resulting in a much lower affinity between Na_v channels and ankB. (C) CK2 phosphorylates four serine residues in the AIS-targeting motif. This increases the affinity of the AIS-targeting motif for the ankyrin MBD by 1,000-fold. It is possible that the density of channels in the axon and at the AIS could be dynamically regulated through increasing or decreasing levels of CK2, or through the activity of yet-to-be identified phosphatases.