Introduction of KCNK1
Potassium channel subfamily K member 1 (KCNK1), also known as inward rectifying potassium channel protein TWIK1, is encoded by the gene KCNK1. Originally cloned from human brain in 1996, KCNK1 is classified into the family of two-pore-domain potassium (K2P) channels, sharing the same overall architecture with four membrane-spanning segments (M1-M4), two pore domains (P1 and P2), involved in the formation of the selectivity filter, and a large extracellular M1P1 loop. Usually, two KCNK1 monomers containing four TMs assemble to form the functional homodimers ion conduction pathway. Beyond the brain, TWIK1 is also expressed at significant levels in other tissues including heart, kidney, pancreas, lung, and placenta. Significantly, TWIK1 is mainly localized in the pericentriolar recycling endosomal compartment in polarized and nonpolarized epithelial cells.
|Basic Information of KCNK1|
|Protein Name||Potassium channel subfamily K member 1|
|Organism||Homo sapiens (Human)|
Function of KCNK1 Membrane Protein
The KCNK1-formed two P-domain K+ (K2P) channels can produce time- and voltage-independent currents opposing membrane depolarization and cell excitability, which is distinctive from many other K+ channels. It is documented that KCNK1 activation is modulated by a diverse array of chemical and physical stimulus including pH, temperature, unsaturated fatty acids, and membrane stretch, etc. As an important component of K2P channels, KCNK1 is proposed to participate in widely physiological processes, such as apoptosis, adrenal gland development, and primary hyperaldosteronism, neuronal excitability and altered motor performance, central O2 chemoreception and breathing control, pain signaling, etc. Strong evidence showed that KCNK1 is functional and contributes to membrane trafficking/expression of transport molecules in the kidney, with impaired regulation of phosphate transport in the proximal tubule and of water transport in the medullary collecting duct in KCNK1 deficient mice. Moreover, KCNK1 is suggested to address to the cell surface when expressed in Xenopus oocytes and combines with a small ubiquitin modifier (SUMO) peptide to its lysine 274 (K274) site, which is responsible for a block of channel activity.
Fig.1 TWIK1 sequence and topological organization. (Chatelain, 2012)
Application of KCNK1 Membrane Protein in Literature
In this article, the authors demonstrated that the K+ selectivity of TWIK1 was modulated by extracellular pH, while at the acidic pH condition found in endosomes, it became permeable to Na+. TWIK1−/− pancreatic β cells are more polarized compared with control, confirming a depolarizing role of TWIK1 in kidney and pancreatic cells.
This article identified TWIK1 could interact with EFA6, an exchange factor for the small G protein ADP-ribosylation factor 6 (ARF6) and the association only occurred after the binding with ARF6. ARF6/EFA6/TWIK1 association played probably an important role in channel internalization and recycling.
This article demonstrated that only the mutation K274E in TWIK1, not K274R, was responsible for an increase of K2P1 current density, suggesting a charge effect of K274E. K274E mutation was the putative sumoylation site, which gave rise to robust current expression in transfected COS-7 cells.
The authors reported that THIK1 could assemble with THIK2 to form active channels via the dominant negative control of pore-mutated subunits, in situ proximity ligation assay, FRET, and electrophysiology of covalent THIK1/THIK2 dimers.
The authors confirmed that TWIK1 could be detected in large and medium-size neurons, independent of TRPV1 or IB4 expression, suggesting involvement of TWIK1 in the maintenance of the pain condition.
KCNK1 Preparation Options
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