Ca(2+)-binding protein centrin 4 is a novel binding partner of rat Eag1 K(+) channels.

Eag1 is neuron-specific K(+) channel abundantly expressed in the brain and retina. Subcellular localization and physiological analyses in neurons reveal that Eag1 may participate in Ca(2+)-signaling processes in the synapse. Here, we searched for rat Eag1 (rEag1)-binding proteins that may contribute to Ca(2+) regulation of the K(+) channel. Yeast two-hybrid screening identified centrin 4, a member of the centrin family of Ca(2+)-binding proteins. GST pull-down and immunoprecipitation assays in brain and retina lysates confirm the interaction of centrin with rEag1 in neurons. Centrin 4 binds to rEag1 in the absence of Ca(2+). Raising Ca(2+) concentration enhances the association efficiency of centrin 4 and rEag1, and is required for the suppression of rEag1 currents by centrin 4. Altogether, our data suggest that centrin 4 is a novel binding partner that may contribute to Ca(2+) regulation of rEag1 in neurons.