Calmodulin Binding to a Novel Site in the AB Module of Kv7.2 Subunits Regulates Surface Expression

Calmodulin (CaM) binding to the AB module underlie multiple mechanisms governing the function of Kv7.2 subunits, which are the main component of the non-inactivating K+ M-current, a key controller of neuronal excitability. Simultaneous binding to helix A and B is crucial for trafficking to the plasma membrane. We have identified a novel CaM-binding site located downstream of helix A, reminiscent of the TW motif of CaM-gated SK2 K+ channels, with W360 as pivotal for surface expression. In the context of the known CaM-binding modes and previous studies, our data suggest a model for traffic control that involves alternative CaM docking to either helix B, the novel TW motif, or the IQ-site of helix A.