Calcium-activated chloride channel
For the Christian private school with the acronym "CLCA", see Christian Life Center Academy.
| Calcium-activated chloride channel | |||||||||
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| Identifiers | |||||||||
| Symbol | CLCA_N | ||||||||
| Pfam | PF08434 | ||||||||
| InterPro | IPR013642 | ||||||||
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The family of calcium-activated chloride channels (CaCCs),[1] which includes chloride channel accessory (CLCA),[2] bestrophin (BEST),[3][4] and certain anoctamin (ANO or TMEM16) channels,[3][4][5][6] are heterogeneous groups of ligand-gated ion channels for chloride that have been identified in many epithelial and endothelial cell types as well as in smooth muscle cells. ANO1 is highly expressed in human gastrointestinal interstitial cells of Cajal, which are proteins which serve as intestinal pacemakers for peristalsis.[5] In addition to their role as chloride channels some CLCA proteins function as adhesion molecules and may also have roles as tumour suppressors.[7]
In humans
CaCCs that are known to occur in humans include:
- Accessories: CLCA1, CLCA2, CLCA3, and CLCA4
- Anoctamins:[note 1] ANO1 and ANO2 (potentially others)[8]
- Bestrophins: BEST1, BEST2, BEST3, and BEST4[8]
Notes
- ↑ The anoctamins are only expressed in eukaryotes, with 10 members in vertebrates.[6] Although all anoctamins are calcium-activated, not all members of this family are ion channels like ANO1; some are phospholipid scramblases.[6] ANO1 was the first anoctamin discovered, with three research groups independently identifying it in 2008.[6] A single protein homologue to the vertebrate anoctamins has been found in fungi and yeast, Aspergillus fumigatus and Saccharomyces cerevisiae, respsectively.[6]
References
- ↑ Hartzell, Criss; Putzler, Ilva; Arreola, Jorge (March 2005). "Calcium-activated Chloride Channels". Annual Review of Physiology 76: 719–58. doi:10.1146/annurev.physiol.67.032003.154341. PMID 15709976.
- ↑ "CLCA1 chloride channel accessory 1 [Homo sapiens (human)]". Gene. National Center for Biotechnology Information. 13 January 2015.
- 1 2 Kunzelmann, K; Kongsuphol, P.; Chootip, K.; et al. (January 2011). "Role of the Ca2+ -activated Cl- channels bestrophin and anoctamin in epithelial cells". Biological Chemistry 392 (1–2): 125–34. doi:10.1515/BC.2011.010. PMID 21194364.
- 1 2 Kunzelmann, K; Kongsuphol, P; Aldehni, F; et al. (October 2009). "Bestrophin and TMEM16-Ca(2+) activated Cl(-) channels with different functions". Cell Calcium 46 (4): 233–41. doi:10.1016/j.ceca.2009.09.003. PMID 19783045.
- 1 2 Sanders, KM; Zhu, MH; Britton, F; et al. (February 2012). "Anoctamins and gastrointestinal smooth muscle excitability". Experimental Physiology 97 (2): 200–6. doi:10.1113/expphysiol.2011.058248. PMC 3272164. PMID 22002868.
- 1 2 3 4 5 Brunner, Janine D.; Lim, Novandy K.; Schenck, Stephen; et al. (11 December 2014). "X-ray structure of a calcium-activated TMEM16 lipid scramblase". Nature 516 (7530): 207–12. doi:10.1038/nature13984.
- ↑ Evans, SR; Thoreson, WB; Beck, CL (2004). "Molecular and functional analyses of two new calcium-activated chloride channel family members from mouse eye and intestine". Journal of Biological Chemistry 279 (40): 41792–800. doi:10.1074/jbc.M408354200. PMC 1383427. PMID 15284223.
- 1 2 "Calcium activated chloride channel". IUPHAR/BPS Guide to Pharmacology. Retrieved 7 October 2015.
The bestrophins encoded by genes BEST1-4 have a topology more consistent with ion channels [9] and form chloride channels that are activated by physiological concentrations of Ca2+, but whether such activation is direct is not known [9]. However, currents generated by bestrophin over-expression do not resemble native CaCC currents. The evidence for and against bestrophin proteins forming CaCC is critically reviewed by Duran et al. in their 2010 paper [5]. Recently, a new gene family, TMEM16 (anoctamin) consisting of 10 members (TMEM16A-K; anoctamin 1–10) has been identified and there is firm evidence that some of these members form chloride channels [4,10]. TMEM16A (anoctamin 1; Ano 1) produces Ca2+-activated Cl- currents with kinetics similar to native CaCC currents recorded from different cell types [2,18-19,21]. ... There are also reports that TMEM16B (anoctamin 2; Ano 2) supports CaCC activity (e.g.[17]) and in TMEM16B(-/-) mice Ca-activated Cl- currents in the main olfactory epithelium (MOE) and in the vomeronasal organ are virtually absent[1]
External links
This article incorporates text from the public domain Pfam and InterPro IPR013642
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