Modulation of Kv4.2 channel expression and gating by dipeptidyl peptidase 10 (DPP10)
Modulation of Kv4.2 channel expression and gating by dipeptidyl peptidase 10 (DPP10)
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DOI：
10.1529/biophysj.104.042358
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发表时间：
2004-10-01
影响因子：
3.4
通讯作者：
Pfaffinger, PJ
中科院分区：
文献类型：
--
作者：
Jerng, HH;Qian, Y;Pfaffinger, PJ
The dipeptidyl aminopeptidase-like protein DPPX (DPP6) associates with Kv4 potassium channels, increasing surface trafficking and reconstituting native neuronal I-SA-like properties. Dipeptidyl peptidase 10 (DPP10) shares with DPP6 a high amino acid identity, lack of enzymatic activity, and expression predominantly in the brain. We used a two-electrode voltage-clamp and oocyte expression system to determine if DPP10 also interacts with Kv4 channels and modulates their expression and function. Kv4.2 coimmunoprecipitated with HA/DPP10 from extracts of oocytes heterologously expressing both proteins. Coexpression with DPP10 and HA/DPP10 enhanced Kv4.2 current by approximately fivefold without increasing protein level. DPP10 also remodeled Kv4.2 kinetic and steady-state properties by accelerating time courses of inactivation and recovery (tau(rec): WT = 200 ms, +DPP10 = 78 ms). Furthermore, DPP10 introduced hyperpolarizing shifts in the conductance-voltage relationship (similar to19 mV) as well as steady-state inactivation (similar to7 mV). The effects of DPP10 on Kv4.1 were similar to Kv4.2; however, distinct biophysical differences were observed. Additional experiments suggested that the cytoplasmic N-terminal domain of DPP10 determines the acceleration of inactivation. In summary, DPP10 is a potent modulator of Kv4 expression and biophysical properties and may be a critical component of somatodendritic I-SA channels in the brain.
