KCNK4
Available structures
PDBOrtholog search: PDBe RCSB
Identifiers
AliasesKCNK4, K2p4.1, TRAAK, TRAAK1, potassium two pore domain channel subfamily K member 4, FHEIG
External IDsOMIM: 605720 MGI: 1298234 HomoloGene: 7391 GeneCards: KCNK4
Orthologs
SpeciesHumanMouse
Entrez

50801

16528

Ensembl

ENSG00000182450

ENSMUSG00000024957

UniProt

Q9NYG8

O88454

RefSeq (mRNA)

NM_016611
NM_033310
NM_001317090

NM_008431

RefSeq (protein)

NP_001304019
NP_201567

NP_032457

Location (UCSC)Chr 11: 64.29 – 64.3 MbChr 19: 6.9 – 6.91 Mb
PubMed search[3][4]
Wikidata
View/Edit HumanView/Edit Mouse

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

References

  1. 1 2 3 GRCh38: Ensembl release 89: ENSG00000182450 - Ensembl, May 2017
  2. 1 2 3 GRCm38: Ensembl release 89: ENSMUSG00000024957 - Ensembl, May 2017
  3. "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
  4. "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
  5. Lesage F, Maingret F, Lazdunski M (April 2000). "Cloning and expression of human TRAAK, a polyunsaturated fatty acids-activated and mechano-sensitive K(+) channel". FEBS Letters. 471 (2–3): 137–140. doi:10.1016/S0014-5793(00)01388-0. PMID 10767409. S2CID 31793244.
  6. Goldstein SA, Bayliss DA, Kim D, Lesage F, Plant LD, Rajan S (December 2005). "International Union of Pharmacology. LV. Nomenclature and molecular relationships of two-P potassium channels". Pharmacological Reviews. 57 (4): 527–540. doi:10.1124/pr.57.4.12. PMID 16382106. S2CID 7356601.
  7. 1 2 "Entrez Gene: KCNK4 potassium channel, subfamily K, member 4".
  8. Patel AJ, Honoré E, Lesage F, Fink M, Romey G, Lazdunski M (May 1999). "Inhalational anesthetics activate two-pore-domain background K+ channels". Nature Neuroscience. 2 (5): 422–426. doi:10.1038/8084. PMID 10321245. S2CID 23092576.
  9. 1 2 Fink M, Lesage F, Duprat F, Heurteaux C, Reyes R, Fosset M, Lazdunski M (June 1998). "A neuronal two P domain K+ channel stimulated by arachidonic acid and polyunsaturated fatty acids". The EMBO Journal. 17 (12): 3297–3308. doi:10.1093/emboj/17.12.3297. PMC 1170668. PMID 9628867.
  10. Vandorpe DH, Morris CE (May 1992). "Stretch activation of the Aplysia S-channel". The Journal of Membrane Biology. 127 (3): 205–214. doi:10.1007/bf00231508. PMID 1495087. S2CID 29622155.
  11. Maingret F, Fosset M, Lesage F, Lazdunski M, Honoré E (January 1999). "TRAAK is a mammalian neuronal mechano-gated K+ channel". The Journal of Biological Chemistry. 274 (3): 1381–1387. doi:10.1074/jbc.274.3.1381. PMID 9880510.
  12. Brohawn SG, Wang W, Handler A, Campbell EB, Schwarz JR, MacKinnon R (November 2019). "The mechanosensitive ion channel TRAAK is localized to the mammalian node of Ranvier". eLife. 8: e50403. doi:10.7554/eLife.50403. PMC 6824864. PMID 31674909.
  13. Brohawn SG, Su Z, MacKinnon R (March 2014). "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. Bibcode:2014PNAS..111.3614B. doi:10.1073/pnas.1320768111. PMC 3948252. PMID 24550493.
  14. Clausen MV, Jarerattanachat V, Carpenter EP, Sansom MS, Tucker SJ (October 2017). "Asymmetric mechanosensitivity in a eukaryotic ion channel". Proceedings of the National Academy of Sciences of the United States of America. 114 (40): E8343–E8351. Bibcode:2017PNAS..114E8343C. doi:10.1073/pnas.1708990114. PMC 5635901. PMID 28923939.
  15. Kanda H, Ling J, Tonomura S, Noguchi K, Matalon S, Gu JG (December 2019). "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. doi:10.1016/j.neuron.2019.08.042. PMC 6895425. PMID 31630908.
  16. O'Donnell AM, Nakamura H, Parekh B, Puri P (December 2019). "Decreased expression of TRAAK channels in Hirschsprung's disease: a possible cause of postoperative dysmotility". Pediatric Surgery International. 35 (12): 1431–1435. doi:10.1007/s00383-019-04572-4. PMID 31542828. S2CID 202718134.
  17. Gripp KW, Smithson SF, Scurr IJ, Baptista J, Majumdar A, Pierre G, et al. (September 2021). "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. doi:10.1038/s41431-021-00818-9. PMC 8440610. PMID 33594261.
  18. Bauer CK, Calligari P, Radio FC, Caputo V, Dentici ML, Falah N, et al. (October 2018). "Mutations in KCNK4 that Affect Gating Cause a Recognizable Neurodevelopmental Syndrome". American Journal of Human Genetics. 103 (4): 621–630. doi:10.1016/j.ajhg.2018.09.001. PMC 6174320. PMID 30290154.
  19. Laigle C, Confort-Gouny S, Le Fur Y, Cozzone PJ, Viola A (2012-12-28). "Deletion of TRAAK potassium channel affects brain metabolism and protects against ischemia". PLOS ONE. 7 (12): e53266. Bibcode:2012PLoSO...753266L. doi:10.1371/journal.pone.0053266. PMC 3532408. PMID 23285272.

Further reading

This article incorporates text from the United States National Library of Medicine, which is in the public domain.

This article is issued from Wikipedia. The text is licensed under Creative Commons - Attribution - Sharealike. Additional terms may apply for the media files.