Evidence for proteasomal degradation of Kv1.5 channel protein.


BACKGROUND The voltage-gated potassium channel Kv1.5 plays a critical role in the maintenance of the membrane potential. While protein degradation is one of the major mechanisms for the regulation of channel functions, little is known on the degradation mechanism of Kv1.5. METHODS AND RESULTS Kv1.5 was expressed in COS cells and its degradation, intracellular localization, and channel activities were assessed by pulse-chase analysis, immunofluorescence, and patch clamp techniques, respectively. Expressed Kv1.5 had a half-life time of approximately 6.7 h, which was prolonged by the proteasome inhibitors of MG132, ALLN, proteasomal inhibitor 1, or lactacystine, but not by a lysosomal inhibitor chloroquine. MG132 increased the protein level of Kv1.5, as well as the level of its ubiquitinated form in a dose-dependent manner. Similar effects of MG132 on endogenous Kv1.5 were seen in cultured rat atrial cells. Within a cell, Kv1.5 was mainly localized in both the endoplasmic reticulum and Golgi apparatus. MG132 increased the immunoreactivity of Kv1.5 in these compartments and also increased Ik(ur) currents through the cell-surface Kv1.5. Pretreatment with either brefeldin A or colchicine abolished MG132-induced increase in Ik(ur) currents. CONCLUSION Kv1.5 is degraded by the proteasome. The inhibition of the proteasome increased Ik(ur) currents secondary to stabilization of the channel protein in the endoplasmic reticulum/Golgi apparatus.

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@article{Kato2005EvidenceFP, title={Evidence for proteasomal degradation of Kv1.5 channel protein.}, author={Masaru Kato and Kazuyoshi Ogura and Junichiro Miake and Norihito Sasaki and Shin-ichi Taniguchi and Osamu Igawa and Akio Yoshida and Yoshiko Hoshikawa and Mitsunobu Murata and Eiji Nanba and Yasutaka Kurata and Yasushi Kawata and Haruaki Ninomiya and Takayuki Morisaki and Masafumi Kitakaze and Ichiro Hisatome}, journal={Biochemical and biophysical research communications}, year={2005}, volume={337 1}, pages={343-8} }