Sodium channels (white) cluster at nodes of Ranvier.

Nodes of Ranvier, the unmyelinated segments of myelinated axons, bear high concentrations of sodium channels to propagate action potentials from node to node. Ratcliffe et al. (page 427) suggest that the sodium channels are recruited to the nodes by interacting through their β subunits with neurofascin, one of the first molecules found in developing nodes of Ranvier.

The interaction of the β subunits with neurofascin, long known to be a cell adhesion molecule in neurons, did not come entirely as a surprise, since β subunits show sequence homology to cell adhesion molecules. This paper provides new evidence that the β subunits of sodium channels perform a dual role: anchoring the sodium channel through lateral interactions in the plasma membrane, as well as their known function of speeding up the opening and closing of sodium channels.

The authors transfected cells in tissue culture to show that neurofascin interacts with the β1 and β3 subunits of sodium channels, but not the β2 subunit, and that the interaction between neurofascin and β1 occurs within the same cell, rather than between adjacent cells. The β1 subunit and neurofascin are both concentrated at nodes of Ranvier in the developing rat brain, as well as in the adult brain. The authors propose that this interaction helps concentrate sodium channels at the nodes of Ranvier. Interestingly, both the β1 subunit and neurofascin bind to ankyrin-G, a protein in the cytoplasm, suggesting that proteins inside the cell guide the assembly of proteins at the node. ▪