Calcium-dependent chloride channel

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TMEM16
Identifiers
Symbol Apoctamin
Pfam PF04547
InterPro IPR032394
TCDB 1.A.17
OPM superfamily 517
OPM protein 4wis

The Calcium-Dependent Chloride Channel (Ca-ClC) proteins (or calcium-activated chloride channels (CaCCs),[1] 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. They include proteins from several structurally different families: chloride channel accessory (CLCA),[2] bestrophin (BEST),[3][4] and calcium-dependent chloride channel anoctamin (ANO or TMEM16) channels]][3][4][5][6] 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] these eukaryotic proteins are "required for normal electrolyte and fluid secretion, olfactory perception, and neuronal and smooth muscle excitability" in animals.[8][9] Members of the Ca-CIC family are generally 600 to 1000 amino acyl residues (aas) in length and exhibit 7 to 10 transmembrane segments (TMSs).

Function[edit]

Tmc1 and Tmc2 (TC#s 1.A.17.4.6 and 1.A.17.4.1, respectively) may play a role in hearing and are required for normal function of cochlear hair cells, possibly as Ca2+ channels or Ca2+ channel subunits (see also family TC# 1.A.82).[10] Mice lacking both channels lack hair cell mechanosensory potentials.[11] There are 8 members of this family in humans, 1 in Drosophila and 2 in C. elegans. One of the latter two is expressed in mechanoreceptors.[12] Tmc1 is a sodium-sensitive cation channel required for salt (Na+) chemosensation in C. elegans "where it is required for salt-evoked neuronal activity and behavioural avoidance of high concentrations of NaCl".[13]

TMEM16A is over-expressed in several tumor types, the role of TMEM16A in gliomas and the potential underlying mechanisms were analyzed by Liu et al. 2014. Knockdown of TMEM16A suppressed cell proliferation, migration and invasion.[14]

The reactions believed to be catalyzed by channels of the Ca-ClC family are:[15]

Cl (out) ⇌ Cl (in)

and

Cations (e.g., Ca2+) (out) ⇌ Cations (e.g., Ca2+) (in)

In humans[edit]

CaCCs that are known to occur in humans include:

See also[edit]

Further reading[edit]

References[edit]

  1. ^ 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]
  1. ^ Hartzell, Criss; Putzler, Ilva; Arreola, Jorge (March 2005). "Calcium-activated Chloride Channels". Annual Review of Physiology. 67: 719–58. doi:10.1146/annurev.physiol.67.032003.154341. PMID 15709976. closed access publication – behind paywall
  2. ^ "CLCA1 chloride channel accessory 1 [Homo sapiens (human)]". Gene. National Center for Biotechnology Information. 13 January 2015. 
  3. ^ a b 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. 
  4. ^ a b 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. 
  5. ^ a b 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 3272164Freely accessible. PMID 22002868. open access publication – free to read
  6. ^ a b c d e 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. PMID 25383531. 
  7. ^ 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 1383427Freely accessible. PMID 15284223. 
  8. ^ Caputo, A; Caci, E; Ferrera, L; et al. (October 2008). "TMEM16A, a membrane protein associated with calcium-dependent chloride channel activity". Science. 322: 590–4. doi:10.1126/science.1163518. PMID 18772398. 
  9. ^ Pang, Chunli; Yuan, Hongbo; Ren, Shuxi; Chen, Yafei; An, Hailong; Zhan, Yong (2014-01-01). "TMEM16A/B associated CaCC: structural and functional insights". Protein and Peptide Letters. 21 (1): 94–99. doi:10.2174/09298665113206660098. ISSN 1875-5305. PMID 24151904. 
  10. ^ Kim, Kyunghee X.; Fettiplace, Robert (2013-01-01). "Developmental changes in the cochlear hair cell mechanotransducer channel and their regulation by transmembrane channel-like proteins". The Journal of General Physiology. 141 (1): 141–148. doi:10.1085/jgp.201210913. ISSN 1540-7748. PMC 3536526Freely accessible. PMID 23277480. 
  11. ^ Kawashima, Yoshiyuki; Géléoc, Gwenaëlle S. G.; Kurima, Kiyoto; Labay, Valentina; Lelli, Andrea; Asai, Yukako; Makishima, Tomoko; Wu, Doris K.; Della Santina, Charles C. (2011-12-01). "Mechanotransduction in mouse inner ear hair cells requires transmembrane channel-like genes". The Journal of Clinical Investigation. 121 (12): 4796–4809. doi:10.1172/JCI60405. ISSN 1558-8238. PMC 3223072Freely accessible. PMID 22105175. 
  12. ^ Smith, Cody J.; Watson, Joseph D.; Spencer, W. Clay; O'Brien, Tim; Cha, Byeong; Albeg, Adi; Treinin, Millet; Miller, David M. (2010-09-01). "Time-lapse imaging and cell-specific expression profiling reveal dynamic branching and molecular determinants of a multi-dendritic nociceptor in C. elegans". Developmental Biology. 345 (1): 18–33. doi:10.1016/j.ydbio.2010.05.502. ISSN 1095-564X. PMC 2919608Freely accessible. PMID 20537990. 
  13. ^ Chatzigeorgiou, Marios; Bang, Sangsu; Hwang, Sun Wook; Schafer, William R. (2013-02-07). "tmc-1 encodes a sodium-sensitive channel required for salt chemosensation in C. elegans". Nature. 494 (7435): 95–99. doi:10.1038/nature11845. ISSN 1476-4687. PMC 4021456Freely accessible. PMID 23364694. 
  14. ^ Liu, Jun; Liu, Yu; Ren, Yingang; Kang, Li; Zhang, Lihua (2014-03-01). "Transmembrane protein with unknown function 16A overexpression promotes glioma formation through the nuclear factor-κB signaling pathway". Molecular Medicine Reports. 9 (3): 1068–1074. doi:10.3892/mmr.2014.1888. ISSN 1791-3004. PMID 24401903. 
  15. ^ "1.A.17 The Calcium-Dependent Chloride Channel (Ca-ClC) Family". TCDB. Retrieved 2016-04-16. 
  16. ^ a b "Calcium activated chloride channel". IUPHAR/BPS Guide to Pharmacology. Retrieved 7 October 2015. 

As of this edit, this article uses content from "1.A.13 The Epithelial Chloride Channel (E-ClC) Family", which is licensed in a way that permits reuse under the Creative Commons Attribution-ShareAlike 3.0 Unported License, but not under the GFDL. All relevant terms must be followed.