Amino acids in the pore region of voltage-gated potassium channels dictate trafficking
Voltage-gated (Kv) potassium channels, which exhibit a high degree of diversity and ubiquity, are fundamental in the control of membrane depolarization and cell excitability. The physiological efficacy of channels is ensured by its abundance and distribution at the cell surface, and is highly controlled by cellular surveillance. Nevertheless, it is not well understood how the regulation system works. In this work it is found that an amino acid pair located in the highly conserved pore region of Kv1 channels, designated as the trafficking code, dictates their trafficking and cell surface expression. The code order for efficient trafficking is Thr/Lys > Thr/Val > Thr/Arg ∼ Thr/His > Ser/Val > Ser/Tyr > Ser/Lys. The trafficking code contains either a positive signal, such as a Thr/Lys pair, which promotes forward trafficking, or a negative signal, such as a Ser/Tyr pair, which induces ER retention. A homomeric Kv1 channel that has a positive trafficking signal travels to the cell surface and has high density. In contrast, a homomeric Kv1 channel that has a negative trafficking signal travels to the cell surface and has low density. For a heteromeric Kv1 channel, the subunit composition governs the trafficking efficiency. The negative trafficking signal in one subunit predominates over the positive signal in another subunit, and the channel travels to the cell surface with altered density compared to homomers. Kv1 trafficking code does not appear to be transferable to other Kv subfamilies due to its readout, which depends on the subenvironment of the Kv1 native pore. Understanding the trafficking of Kv1 channels gives insight into the cellular regulation of membrane protein expression and localization and provides a molecular basis for dealing with inherited human diseases caused by ion channel trafficking deficiency.
Molecular biology|Neurology|Cellular biology
Zhu, Jing, "Amino acids in the pore region of voltage-gated potassium channels dictate trafficking" (2007). ETD Collection for Fordham University. AAI3301443.