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.
The dipeptidyl aminopeptidase-like protein 6, β-subunit, Dpp6, DPPX-S or DPLP (865 aas) of the Kv4.2 K+ channel (TC# 1.A.1.2.5; Dougherty et al. 2009). DPPX-S destabilizes resting and intermediate states in the voltage-dependent activation pathway, which promotes the outward gating charge movement (Dougherty and Covarrubias 2006).
Dpp6 of Homo sapiens
The inactive dipeptidyl peptidase or prolyl oligopeptidase, DPP10, DPRP-3, DPL2, DPPIV or DPR3 of 798 aas and 1 N-terminal TMS. It has an N-terminal DPPIV_N domain and a C-terminal Abhydrolase domain. It is an inactivating modulator of Kv4 channels and the Kv1.4 channel (Kuo et al. 2017). DPP10 and KChIP2b (Q9NS61; TC# 5.B.1.2.2) both modulate Kv4.3 inactivation, but their primary effects are on different inactivation states. Thus DPP10 may be a general modulator of voltage-gated K+ channel inactivation (Kuo et al. 2017).
DPP10 of Homo sapiens
Dipeptide peptidease, DPP8 of 1452 aas.
DPP8 of Trichinella patagoniensis
Peptidase S9B dipeptidylpeptidase IV domain protein of 691 aas
Peptidase S9B of Rhodopirellula sp. SWK7