Biology:KCNK4
 Generic protein structure example |
Potassium channel subfamily K member 4 is a protein that in humans is encoded by the KCNK4 gene.[1][2][3] 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.[3]
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.[4]
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.[5] The highest levels of TRAAK expression are in the olfactory system, cerebral cortex, hippocampal formation, habenula, basal ganglia, and cerebellum.[5] 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.[6][7]
TRAAK channels play a critical role in the maintenance of the resting membrane potential in excitable cell types.[8] 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.[9] 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.[10] 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.[11] 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.[12][13] Animal models containing known syndromic KCNK4 mutations have recapitulated these phenotypic abnormalities.[14] High TRAAK channel density has also been implicated in the resulting cerebral ischemia following the event of a stroke.[15]
See also
- Tandem pore domain potassium channel
References
- ↑ "Cloning and expression of human TRAAK, a polyunsaturated fatty acids-activated and mechano-sensitive K(+) channel". FEBS Letters 471 (2–3): 137–140. April 2000. doi:10.1016/S0014-5793(00)01388-0. PMID 10767409.
- ↑ "International Union of Pharmacology. LV. Nomenclature and molecular relationships of two-P potassium channels". Pharmacological Reviews 57 (4): 527–540. December 2005. doi:10.1124/pr.57.4.12. PMID 16382106. https://escholarship.org/uc/item/3k15p5vt.
- ↑ 3.0 3.1 "Entrez Gene: KCNK4 potassium channel, subfamily K, member 4". https://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=50801.
- ↑ "Inhalational anesthetics activate two-pore-domain background K+ channels". Nature Neuroscience 2 (5): 422–426. May 1999. doi:10.1038/8084. PMID 10321245.
- ↑ 5.0 5.1 "A neuronal two P domain K+ channel stimulated by arachidonic acid and polyunsaturated fatty acids". The EMBO Journal 17 (12): 3297–3308. June 1998. doi:10.1093/emboj/17.12.3297. PMID 9628867.
- ↑ "Stretch activation of the Aplysia S-channel". The Journal of Membrane Biology 127 (3): 205–214. May 1992. doi:10.1007/bf00231508. PMID 1495087.
- ↑ "TRAAK is a mammalian neuronal mechano-gated K+ channel". The Journal of Biological Chemistry 274 (3): 1381–1387. January 1999. doi:10.1074/jbc.274.3.1381. PMID 9880510.
- ↑ "The mechanosensitive ion channel TRAAK is localized to the mammalian node of Ranvier". eLife 8: e50403. November 2019. doi:10.7554/eLife.50403. PMID 31674909.
- ↑ "Mechanosensitivity is mediated directly by the lipid membrane in TRAAK and TREK1 K+ channels". Proceedings of the National Academy of Sciences of the United States of America 111 (9): 3614–3619. March 2014. doi:10.1073/pnas.1320768111. PMID 24550493. Bibcode: 2014PNAS..111.3614B.
- ↑ "Asymmetric mechanosensitivity in a eukaryotic ion channel". Proceedings of the National Academy of Sciences of the United States of America 114 (40): E8343–E8351. October 2017. doi:10.1073/pnas.1708990114. PMID 28923939. Bibcode: 2017PNAS..114E8343C.
- ↑ "TREK-1 and TRAAK Are Principal K+ Channels at the Nodes of Ranvier for Rapid Action Potential Conduction on Mammalian Myelinated Afferent Nerves". Neuron 104 (5): 960–971.e7. December 2019. doi:10.1016/j.neuron.2019.08.042. PMID 31630908.
- ↑ "Decreased expression of TRAAK channels in Hirschsprung's disease: a possible cause of postoperative dysmotility". Pediatric Surgery International 35 (12): 1431–1435. December 2019. doi:10.1007/s00383-019-04572-4. PMID 31542828.
- ↑ "Syndromic disorders caused by gain-of-function variants in KCNH1, KCNK4, and KCNN3-a subgroup of K+ channelopathies". European Journal of Human Genetics 29 (9): 1384–1395. September 2021. doi:10.1038/s41431-021-00818-9. PMID 33594261.
- ↑ "Mutations in KCNK4 that Affect Gating Cause a Recognizable Neurodevelopmental Syndrome". American Journal of Human Genetics 103 (4): 621–630. October 2018. doi:10.1016/j.ajhg.2018.09.001. PMID 30290154.
- ↑ "Deletion of TRAAK potassium channel affects brain metabolism and protects against ischemia". PLOS ONE 7 (12): e53266. 2012-12-28. doi:10.1371/journal.pone.0053266. PMID 23285272. Bibcode: 2012PLoSO...753266L.
Further reading
- "Potassium leak channels and the KCNK family of two-P-domain subunits". Nature Reviews. Neuroscience 2 (3): 175–184. March 2001. doi:10.1038/35058574. PMID 11256078. https://escholarship.org/uc/item/9z7112ns.
- "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. October 2000. doi:10.1016/S0169-328X(00)00183-2. PMID 11042359.
- "DNA cloning using in vitro site-specific recombination". Genome Research 10 (11): 1788–1795. November 2000. doi:10.1101/gr.143000. PMID 11076863.
- "The neuroprotective agent sipatrigine (BW619C89) potently inhibits the human tandem pore-domain K(+) channels TREK-1 and TRAAK". Brain Research 892 (1): 94–101. February 2001. doi:10.1016/S0006-8993(00)03239-X. PMID 11172753.
- "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. March 2001. doi:10.1101/gr.GR1547R. PMID 11230166.
- "Systematic subcellular localization of novel proteins identified by large-scale cDNA sequencing". EMBO Reports 1 (3): 287–292. September 2000. doi:10.1093/embo-reports/kvd058. PMID 11256614.
- "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. June 2002. doi:10.1016/S0169-328X(02)00157-2. PMID 12191490.
- "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. December 2002. doi:10.1073/pnas.242603899. PMID 12477932. Bibcode: 2002PNAS...9916899M.
- "An unappreciated role for RNA surveillance". Genome Biology 5 (2): R8. 2005. doi:10.1186/gb-2004-5-2-r8. PMID 14759258.
- "Trichloroethanol enhances the activity of recombinant human TREK-1 and TRAAK channels". Neuropharmacology 46 (5): 750–760. April 2004. doi:10.1016/j.neuropharm.2003.11.023. PMID 14996553.
- "From ORFeome to biology: a functional genomics pipeline". Genome Research 14 (10B): 2136–2144. October 2004. doi:10.1101/gr.2576704. PMID 15489336.
- "Diversification of transcriptional modulation: large-scale identification and characterization of putative alternative promoters of human genes". Genome Research 16 (1): 55–65. January 2006. doi:10.1101/gr.4039406. PMID 16344560.
- "The LIFEdb database in 2006". Nucleic Acids Research 34 (Database issue): D415–D418. January 2006. doi:10.1093/nar/gkj139. PMID 16381901.
External links
- KCNK4+protein,+human at the US 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.
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