8.A.51 The Dipeptidyl-aminopeptidase-like Protein 6 beta subunit of Kv4 channels (DPP6) Family
Auxiliary beta-subunits dictate the physiological properties of voltage-gated K+ (KV) channels in excitable tissues. The dipeptidyl-aminopeptidase-like protein 6 (DPP6) is a specific beta-subunit of neuronal KV4 channels, which may promote gating through interactions between the single transmembrane segment of DPP6 and the channel's voltage sensing domain (VSD). A combination of gating current measurements and protein biochemistry (in-vitro translation and co- immunoprecipitations) revealed preferential physical interaction between the isolated KV4.2-VSD and DPP6 (Dougherty et al. 2009). Significantly weaker interactions were detected between DPP6 and KV1.3 channels or the KV4.2 pore domain. More efficient gating charge movement resulting from a direct interaction between DPP6 and the KV4.2-VSD is unique among the known actions of KV channel beta-subunits. Thus. the modular VSD of a KV channel can be directly regulated by transmembrane protein-protein interactions involving an extrinsic beta-subunit. Understanding these interactions may shed light on the pathophysiology of recently identified human disorders associated with mutations affecting the dpp6 gene.