KCNK4
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Potassium channel subfamily K member 4 is a protein that in humans is encoded by the KCNK4 gene.[5][6][7] KCNK4 protein channels are also called TRAAK channels.
Function
KNCK4 is a gene segment that encodes for the TRAAK (TWIK-related Arachidonic Acid-Stimulated K+) subfamily of mechanosensitive potassium channels. Potassium channels play a role in many cellular processes including action potential depolarization, muscle contraction, hormone secretion, osmotic regulation, and ion flow. The K2P4.1 protein is a lipid-gated ion channel that belongs to the superfamily of potassium channel proteins containing two pore-forming P domains (K2P). K2P4.1 homodimerizes and functions as an outwardly rectifying channel. It is expressed primarily in neural tissues and is stimulated by membrane stretch and polyunsaturated fatty acids.[7]
TRAAK channels are found in mammalian neurons and are part of a protein family of weakly inward rectifying potassium channels. This subfamily of potassium channels is mechanically gated. The C-terminal of TRAAK has a charged cluster that is important in maintaining the mechanosensitive properties of the channel.[8]
TRAAK is only expressed in neuronal tissue, and can be found in the brain, spinal cord, and retina, which suggests that it has a function beyond mechanotransduction in terms of neuronal excitability.[9] The highest levels of TRAAK expression are in the olfactory system, cerebral cortex, hippocampal formation, habenula, basal ganglia, and cerebellum.[9] TRAAK channels are mechanically activated when there is a convex curvature in the membrane that alters the channel’s activity. TRAAK channels are thought to have a role in axonal pathfinding, growth cone motility, and neurite elongation, as well as possibly having a role in touch or pain detection.[10][11]
TRAAK channels play a critical role in the maintenance of the resting membrane potential in excitable cell types.[12] More recently, TRAAK channels have been identified as an integral component of the nervous system, contributing to a variety of important biological functions such as: neurite migration, neurotransmission, and signal transduction across several sensory modalities.[13] TRAAK and related mechanosensitive ion channels initiate these and other complex physiological processes by detecting asymmetrical pressure gradients generated across the inner and outer leaflets of the cell membrane, characterizing a rich profile of mechanical bilayer interactions.[14] Furthermore, KCNK4 expression patterns the axonal segments of neurons in both central and peripheral nervous systems by inserting TRAAK membrane protein channels at the Nodes of Ranvier and allowing for saltatory conduction.[15] The pathologies that are associated with improper KCNK4 expression such as Hirchsprung's Disease and FHEIG (facial dysmorphism, hypertrichosis, epilepsy, developmental/ID delay, and gingival overgrowth) syndrome, manifest accordingly as a constellation of neurological symptoms resulting from neuronal dysplasia.[16][17] Animal models containing known syndromic KCNK4 mutations have recapitulated these phenotypic abnormalities.[18] High TRAAK channel density has also been implicated in the resulting cerebral ischemia following the event of a stroke.[19]
See also
- Tandem pore domain potassium channel
References
- ^ a b c GRCh38: Ensembl release 89: ENSG00000182450 – Ensembl, May 2017
- ^ a b c GRCm38: Ensembl release 89: ENSMUSG00000024957 – Ensembl, May 2017
- ^ "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
- ^ "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
- S2CID 31793244.
- S2CID 7356601.
- ^ a b "Entrez Gene: KCNK4 potassium channel, subfamily K, member 4".
- S2CID 23092576.
- ^ PMID 9628867.
- S2CID 29622155.
- PMID 9880510.
- PMID 31674909.
- PMID 24550493.
- PMID 28923939.
- PMID 31630908.
- S2CID 202718134.
- PMID 33594261.
- PMID 30290154.
- PMID 23285272.
Further reading
- Goldstein SA, Bockenhauer D, O'Kelly I, Zilberberg N (March 2001). "Potassium leak channels and the KCNK family of two-P-domain subunits". Nature Reviews. Neuroscience. 2 (3): 175–184. S2CID 9682396.
- Chapman CG, Meadows HJ, Godden RJ, Campbell DA, Duckworth M, Kelsell RE, et al. (October 2000). "Cloning, localisation and functional expression of a novel human, cerebellum specific, two pore domain potassium channel". Brain Research. Molecular Brain Research. 82 (1–2): 74–83. PMID 11042359.
- Hartley JL, Temple GF, Brasch MA (November 2000). "DNA cloning using in vitro site-specific recombination". Genome Research. 10 (11): 1788–1795. PMID 11076863.
- Meadows HJ, Chapman CG, Duckworth DM, Kelsell RE, Murdock PR, Nasir S, et al. (February 2001). "The neuroprotective agent sipatrigine (BW619C89) potently inhibits the human tandem pore-domain K(+) channels TREK-1 and TRAAK". Brain Research. 892 (1): 94–101. S2CID 37830674.
- Wiemann S, Weil B, Wellenreuther R, Gassenhuber J, Glassl S, Ansorge W, et al. (March 2001). "Toward a catalog of human genes and proteins: sequencing and analysis of 500 novel complete protein coding human cDNAs". Genome Research. 11 (3): 422–435. PMID 11230166.
- Simpson JC, Wellenreuther R, Poustka A, Pepperkok R, Wiemann S (September 2000). "Systematic subcellular localization of novel proteins identified by large-scale cDNA sequencing". EMBO Reports. 1 (3): 287–292. PMID 11256614.
- Ozaita A, Vega-Saenz de Miera E (June 2002). "Cloning of two transcripts, HKT4.1a and HKT4.1b, from the human two-pore K+ channel gene KCNK4. Chromosomal localization, tissue distribution and functional expression". Brain Research. Molecular Brain Research. 102 (1–2): 18–27. PMID 12191490.
- Strausberg RL, Feingold EA, Grouse LH, Derge JG, Klausner RD, Collins FS, et al. (December 2002). "Generation and initial analysis of more than 15,000 full-length human and mouse cDNA sequences". Proceedings of the National Academy of Sciences of the United States of America. 99 (26): 16899–16903. PMID 12477932.
- Hillman RT, Green RE, Brenner SE (2005). "An unappreciated role for RNA surveillance". Genome Biology. 5 (2): R8. PMID 14759258.
- Harinath S, Sikdar SK (April 2004). "Trichloroethanol enhances the activity of recombinant human TREK-1 and TRAAK channels". Neuropharmacology. 46 (5): 750–760. S2CID 10938867.
- Wiemann S, Arlt D, Huber W, Wellenreuther R, Schleeger S, Mehrle A, et al. (October 2004). "From ORFeome to biology: a functional genomics pipeline". Genome Research. 14 (10B): 2136–2144. PMID 15489336.
- Kimura K, Wakamatsu A, Suzuki Y, Ota T, Nishikawa T, Yamashita R, et al. (January 2006). "Diversification of transcriptional modulation: large-scale identification and characterization of putative alternative promoters of human genes". Genome Research. 16 (1): 55–65. PMID 16344560.
- Mehrle A, Rosenfelder H, Schupp I, del Val C, Arlt D, Hahne F, et al. (January 2006). "The LIFEdb database in 2006". Nucleic Acids Research. 34 (Database issue): D415–D418. PMID 16381901.
External links
- KCNK4+protein,+human at the U.S. National Library of Medicine Medical Subject Headings (MeSH)
This article incorporates text from the United States National Library of Medicine, which is in the public domain.