Ankyrin-G (green) helps cluster βIV spectrin (red) and others.

Axon initial segments are specialized microdomains that integrate neuronal inputs and initiate action potentials. On page 739, Jenkins and Bennett demonstrate that the ankyrin-G adaptor protein is required to coordinate the assembly of the initial segment during early development, and suggest that related mechanisms may regulate the assembly of other microdomains in a variety of cell types.Concentrated in axon initial segments are both voltage-gated sodium channels and several proteins that have been hypothesized to direct the assembly of the microdomain. In the new work, the authors examined protein localization in Purkinje neuron initial segments during development in wild-type and ankyrin-G mutant mice. Ankyrin-G and βIV spectrin appear at axon initial segments by postnatal day 2, but the sodium channels and adhesion molecules are not fully assembled in the microdomain until seven days later. In mice lacking cerebellar ankyrin-G, βIV spectrin and other components of the microdomain fail to cluster in the axon initial segments.

The results imply that ankyrin-G directs the assembly of voltage-gated sodium channels, βIV spectrin, and adhesion molecules in the axon initial segment to form this critical microdomain. The presence of ankyrin-G in other microdomains, such as neuromuscular junctions and the basolateral domains of epithelial cells, suggests that it may function similarly elsewhere. ▪