Bréchet et al.
Action potentials shoot down axons thanks to a wave of membrane depolarization that triggers specialized membrane regions at the start of the axon—the axon initial segment (AIS)—and at regular intervals along the axon corresponding to gaps in the myelin sheath—the nodes of Ranvier. These specialized regions are characterized by a local clustering of sodium channels.
The clustering requires binding of the sodium channels to a cytoskeletal protein called ankyrin G, also spatially restricted to the AIS and nodes of Ranvier. However, ankyrin G has a homologous protein called ankyrin B that localizes to different parts of the neuron. Given that sodium channels can bind to either ankyrin in vitro, what makes the channels preferentially bind to ankyrin G in vivo?
To answer this question, Bréchet et al. homed in on the precise residues in sodium channels that are required for the interaction with ankyrin G. They pinpointed a sequence of residues that looked like a target for phosphorylation by CK2, and sure enough, it was. CK2 phosphorylated the sodium channels and this was required for the channels' correct positioning along the axon membrane.
In vitro, however, phosphorylation by CK2 prompted the channels to bind both ankyrin G and B. The clue to the sodium channels' specificity for ankyrin G came when the team looked at the distribution of CK2 in neurons and found that it was also restricted to the AIS and the nodes of Ranvier. The big question now is, what targets CK2? RW