Silent but not dumb: how cellular trafficking and pore gating modulate expression of TWIK1 and THIK2.

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Citation

Bichet D, Blin S, Feliciangeli S, Chatelain FC, Bobak N, Lesage F

Silent but not dumb: how cellular trafficking and pore gating modulate expression of TWIK1 and THIK2.

Pflugers Arch. 2015 May;467(5):1121-31. doi: 10.1007/s00424-014-1631-y. Epub 2014 Oct 24.

PubMed ID
25339226 [ View in PubMed
]
Abstract

Among K2P channels, a few of them turned out to be difficult to express in heterologous systems and were coined "silent subunits". Recent studies have shed light on the mechanisms behind this apparent lack of channel activity at the plasma membrane. For TWIK1 and THIK2 channels, silence is related to a combination of intracellular retention and low intrinsic activity. TWIK1 is constitutively endocytosed from the plasma membrane before being transported to recycling endosomes, whereas THIK2 is restricted to endoplasmic reticulum. These intracellular localizations are related to trafficking signals located in the cytoplasmic parts of the channels. When these motifs are mutated or masked, channels are redistributed at the plasma membrane and produce measurable currents. However, these currents are of modest amplitude. This weak basal activity is due to a hydrophobic barrier in the deep pore that limits water and ions in the conduction pathway. Other silent channels KCNK7, TWIK2, and TASK5 are still under study. Expression and characterization of these K2P channels pave the way for a better understanding of the mechanisms controlling intracellular trafficking of membrane proteins, ion conduction, and channel gating.

DrugBank Data that Cites this Article

Polypeptides
NameUniProt ID
Potassium channel subfamily K member 1O00180Details