Open AccessFly DPP10 acts as a channel ancillary subunit and possesses peptidase activity
Author(s) -
Yohei Shiina,
Toshitaka Muto,
Zhili Zhang,
Ahmad Baihaqie,
Takumi Yoshizawa,
Hye-in J. Lee,
Eulsoon Park,
Shinya Tsukiji,
Koichi Takimoto
Publication year - 2016
Publication title -
scientific reports
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.24
H-Index - 213
ISSN - 2045-2322
DOI - 10.1038/srep26290
Subject(s) - protein subunit , dipeptidyl peptidase , gating , potassium channel , substrate (aquarium) , biochemistry , biology , enzyme , biophysics , gene , ecology
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 K m values towards this substrate. However, fly DPP10 exhibits approximately a 6-times-lower relative k cat 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.