Effect of Phosphorylation on the Interaction between Sodium Channels and Ankyrin

Abstract

Voltage-dependent sodium channels(NaChs) are distributed at the nodes of Ranvier in myelinated axons which are critical for generation and propagation of neural signal´. The nodal distribution of NaChs is partly maintained by linkage between NaChs and axolemmal cytoskeletal protein, ankyrin´. To study how this linkage is regulated, we tested the effect of phosphorylation on their interaction because phosphorylation has been known to modulate interaction between proteins2-5. NaChs and ankyrin were purified from rat brain and human red blood cells, respectively. Ankyrin was iodinated and both NaChs and iodinated ankyrin were phosphorylated by cAMP-dependent protein kinase. The radioactivity of iodinated ankyrin bound to NaChs was measured. Phosphorylation of each protein decreased the interaction, and particularly, phosphorylation of ankyrin had a greater effect than that of NaChs. Phosphorylation of both proteins had an additive effect. These results suggest that phosphorylation may be involved in regulation of the interaction between NaChs and ankyrin.