A MAGUK Enhances EAG Potassium Channel Function

Adaptor proteins, by bringing together kinases and other effectors, form a submembrane scaffold of signaling molecules. One such adaptor, Drosophila Camguk (CMG), is a member of the membrane-associated guanylate kinase family and associates with calciumand calmodulin-dependent protein kinase II (CaMKII). This week, Marble et al. describe a signaling complex including CMG, CaMKII, and the Ether-á-go-go (EAG) potassium channel, the Drosophila ortholog of KCNH1. Phosphorylation of EAG by CaMKII leads to a significant increase in current. Previous studies have reported that eag mutants or CaMKII inhibition cause similar associative learning deficits in Drosophila; thus the authors looked for a functional link between the adaptor molecule and the potassium channel. When CMG and EAG were coexpressed in Xenopus oocytes, whole-cell currents doubled compared with EAG alone. The increase depended on threonine 787, the residue phosphorylated by CaMKII, although the CMG–EAG interaction itself involved a separate domain. The results suggest that CMG, probably indirectly through CaMKII, enhances EAG phosphorylation and thus increases surface expression.