期刊
CHANNELS
卷 3, 期 2, 页码 122-128出版社
LANDES BIOSCIENCE
DOI: 10.4161/chan.3.2.8333
关键词
gating charge movement; voltage-sensing domain; pore domain; voltage-dependent gating; DPP6; K(V)1.3
资金
- National Institutes of Health, USA [R01 NS032337-13, GM52302, T32 AA007463-22]
- Thomas Jefferson University
Auxiliary beta-subunits dictate the physiological properties of voltage-gated K+ (K-V) channels in excitable tissues. In many instances, however, the underlying mechanisms of action are poorly understood. The dipeptidyl-aminopeptidase-like protein 6 (DPP6) is a specific beta-subunit of neuronal K(V)4 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 K(V)4.2-VSD and DPP6. Significantly weaker interactions were detected between DPP6 and K(V)1.3 channels or the K(V)4.2 pore domain. More efficient gating charge movement resulting from a direct interaction between DPP6 and the K(V)4.2- VSD is unique among the known actions of KV channel beta-subunits. This study shows that 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.
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