Transmembrane interaction mediates complex formation between peptidase homologues and Kv4 channels.
An asthma-related peptidase homologue (DPP10) may act as an auxiliary subunit of Kv4 channels, similar to DPPX. Here we show that DPP10 preferentially binds to Kv4 channel proteins to increase current density and alter channel gating. DPP10 also forms complexes by themselves and with DPPX in the absence of Kv4 channels. DPP10 mRNA is abundantly expressed in nodose and dorsal root ganglia, suggesting that DPP10 participates in controlling airway reactivity and mechanosensation. The region from the N-terminus to the end of the transmembrane of DPP10 mediates its association with the channel, whereas the S1-S2 portion of the channel is sufficient for complex formation. This N-terminal portion of DPP10 also confers all the gating effects produced by the peptidase homologue. Thus, interaction between transmembranes of DPP10/DPPX and Kv4 channel mediates functional complex formation. We call this protein DPPY, instead of DPP10, because of its revealed role as a Kv4 channel regulator.
Ren
Xiaomeng
X
Department of Environmental and Occupational Health, Graduate School of Public Health, University of Pittsburgh, 3343 Forbes Avenue, Pittsburgh, PA 15260, USA.
Hayashi
Yukio
Y
Yoshimura
Naoki
N
Takimoto
Koichi
K
D017398:Alternative Splicing / Q000502:physiology; D000818:Animals; D016466:CHO Cells; D002462:Cell Membrane / Q000378:metabolism*; D006224:Cricetinae; D004152:Dipeptidyl-Peptidases and Tripeptidyl-Peptidases / Q000235:genetics / Q000378:metabolism*; D005727:Ganglia, Spinal / Q000378:metabolism; D006801:Humans; D015640:Ion Channel Gating / Q000502:physiology; D046911:Macromolecular Substances / Q000378:metabolism; D008297:Male; D008969:Molecular Sequence Data; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000378:metabolism*; D009475:Neurons, Afferent / Q000378:metabolism; D009620:Nodose Ganglion / Q000378:metabolism; D015221:Potassium Channels / Q000235:genetics / Q000378:metabolism*; D024642:Potassium Channels, Voltage-Gated / Q000378:metabolism*; D020033:Protein Isoforms / Q000235:genetics / Q000378:metabolism; D021122:Protein Subunits / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D017386:Sequence Homology, Amino Acid; D051672:Shal Potassium Channels
D046911:Macromolecular Substances; D009419:Nerve Tissue Proteins; D015221:Potassium Channels; D024642:Potassium Channels, Voltage-Gated; D020033:Protein Isoforms; D021122:Protein Subunits; D051672:Shal Potassium Channels; C476879:DPP10 protein, human; C557320:DPP6 protein, rat; D004152:Dipeptidyl-Peptidases and Tripeptidyl-Peptidases