title: Fly DPP10 acts as a channel ancillary subunit and possesses peptidase activity.
abstract: Mammalian DPP6 (DPPX) and DPP10 (DPPY) belong to a family of dipeptidyl peptidases, but lack enzyme activity. Instead, these proteins form complexes with voltage-gated K(+) channels in Kv4 family to control their gating and other properties. Here, we find that the fly DPP10 ortholog acts as an ancillary subunit of Kv4 channels and digests peptides. Similarly to mammalian DPP10, the fly ortholog tightly binds to rat Kv4.3 protein. The association causes negative shifts in voltage dependence of channel activation and steady state inactivation. It also results in faster inactivation and recovery from inactivation. In addition to its channel regulatory role, fly DPP10 exhibits significant dipeptidyl peptidase activity with Gly-Pro-MCA (glycyl-L-proline 4-methylcoumaryl-7-amide) as a substrate. Heterologously expressed Flag-tagged fly DPP10 and human DPP4 show similar Km values towards this substrate. However, fly DPP10 exhibits approximately a 6-times-lower relative kcat value normalized with anti-Flag immunoreactivity than human DPP4. These results demonstrate that fly DPP10 is a dual functional protein, controlling Kv4 channel gating and removing bioactive peptides.
authors.affiliation: Department of Bioengineering, Nagaoka University of Technology, 1603-1 Kamitomioka, Nagaoka, Niigata 940-2188, Japan.
authors.forename: Yohei
authors.initials: Y
authors.lastname: Shiina
authors.affiliation: Department of Bioengineering, Nagaoka University of Technology, 1603-1 Kamitomioka, Nagaoka, Niigata 940-2188, Japan.
authors.forename: Tomohiro
authors.initials: T
authors.lastname: Muto
authors.affiliation: Department of Bioengineering, Nagaoka University of Technology, 1603-1 Kamitomioka, Nagaoka, Niigata 940-2188, Japan.
authors.forename: Zhili
authors.initials: Z
authors.lastname: Zhang
authors.affiliation: Department of Bioengineering, Nagaoka University of Technology, 1603-1 Kamitomioka, Nagaoka, Niigata 940-2188, Japan.
authors.forename: Ahmad
authors.initials: A
authors.lastname: Baihaqie
authors.affiliation: Department of Bioengineering, Nagaoka University of Technology, 1603-1 Kamitomioka, Nagaoka, Niigata 940-2188, Japan.
authors.forename: Takamasa
authors.initials: T
authors.lastname: Yoshizawa
authors.affiliation: Department of Bioengineering, Nagaoka University of Technology, 1603-1 Kamitomioka, Nagaoka, Niigata 940-2188, Japan.
authors.forename: Hye-In J
authors.initials: HI
authors.lastname: Lee
authors.affiliation: Department of Bioengineering, Nagaoka University of Technology, 1603-1 Kamitomioka, Nagaoka, Niigata 940-2188, Japan.
authors.forename: Eulsoon
authors.initials: E
authors.lastname: Park
authors.affiliation: Frontier Research Institute for Materials Science, Nagoya Institute of Technology, Gokiso-cho, Showa-ku, Nagoya 466-855, Japan.|Department of Materials Science and Engineering, Nagoya Institute of Technology, Gokiso-cho, Showa-ku, Nagoya 466-855, Japan.
authors.forename: Shinya
authors.initials: S
authors.lastname: Tsukiji
authors.affiliation: Department of Bioengineering, Nagaoka University of Technology, 1603-1 Kamitomioka, Nagaoka, Niigata 940-2188, Japan.
authors.forename: Koichi
authors.initials: K
authors.lastname: Takimoto
mesh_terms: D000818:Animals; D003374:Coumarins / Q000378:metabolism; D004151:Dipeptides / Q000378:metabolism; D004152:Dipeptidyl-Peptidases and Tripeptidyl-Peptidases / Q000235:genetics / Q000502:physiology*; D029721:Drosophila Proteins / Q000235:genetics / Q000502:physiology*; D004331:Drosophila melanogaster / Q000201:enzymology*; D006801:Humans; D051605:Kv Channel-Interacting Proteins / Q000502:physiology*; D024642:Potassium Channels, Voltage-Gated / Q000502:physiology; D011485:Protein Binding; D021122:Protein Subunits / Q000502:physiology; D059748:Proteolysis; D051381:Rats
chemical_list: D003374:Coumarins; D004151:Dipeptides; D029721:Drosophila Proteins; D051605:Kv Channel-Interacting Proteins; D024642:Potassium Channels, Voltage-Gated; D021122:Protein Subunits; C057970:glycylprolyl-4-methylcoumaryl-7-amide; C000629344:CG11319 protein, Drosophila; D004152:Dipeptidyl-Peptidases and Tripeptidyl-Peptidases