Calcium-dependent chloride channel explained

Symbol:Apoctamin
TMEM16
Pfam:PF04547
Interpro:IPR032394
Tcdb:1.A.17
Opm Family:369
Membranome Superfamily:219

The Calcium-Dependent Chloride Channel (Ca-ClC) proteins (or calcium-activated chloride channels (CaCCs), 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), bestrophin (BEST), and calcium-dependent chloride channel anoctamin (ANO or TMEM16) channels ANO1 is highly expressed in human gastrointestinal interstitial cells of Cajal, which are proteins which serve as intestinal pacemakers for peristalsis. In addition to their role as chloride channels some CLCA proteins function as adhesion molecules and may also have roles as tumour suppressors. These eukaryotic proteins are "required for normal electrolyte and fluid secretion, olfactory perception, and neuronal and smooth muscle excitability" in animals.[1] [2] 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

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).[3] Mice lacking both channels lack hair cell mechanosensory potentials.[4] 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.[5] 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".[6]

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.[7]

The reactions believed to be catalyzed by channels of the Ca-ClC family are:[8]

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

In humans

s that are known to occur in humans include:

See also

Further reading

Notes and References

  1. Caputo A, Caci E, Ferrera L, Pedemonte N, Barsanti C, Sondo E, Pfeffer U, Ravazzolo R, Zegarra-Moran O, Galietta LJ . TMEM16A, a membrane protein associated with calcium-dependent chloride channel activity . Science . 322 . 5901 . 590–4 . October 2008 . 18772398 . 10.1126/science.1163518 . 2008Sci...322..590C . 52870095 . free .
  2. Pang C, Yuan H, Ren S, Chen Y, An H, Zhan Y . TMEM16A/B associated CaCC: structural and functional insights . Protein and Peptide Letters . 21 . 1 . 94–9 . 2014-01-01 . 24151904 . 10.2174/09298665113206660098 .
  3. Kim KX, Fettiplace R . Developmental changes in the cochlear hair cell mechanotransducer channel and their regulation by transmembrane channel-like proteins . The Journal of General Physiology . 141 . 1 . 141–8 . January 2013 . 23277480 . 3536526 . 10.1085/jgp.201210913 .
  4. Kawashima Y, Géléoc GS, Kurima K, Labay V, Lelli A, Asai Y, Makishima T, Wu DK, Della Santina CC, Holt JR, Griffith AJ . Mechanotransduction in mouse inner ear hair cells requires transmembrane channel-like genes . The Journal of Clinical Investigation . 121 . 12 . 4796–809 . December 2011 . 22105175 . 3223072 . 10.1172/JCI60405 .
  5. Smith CJ, Watson JD, Spencer WC, O'Brien T, Cha B, Albeg A, Treinin M, Miller DM . 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 . September 2010 . 20537990 . 2919608 . 10.1016/j.ydbio.2010.05.502 .
  6. Chatzigeorgiou M, Bang S, Hwang SW, Schafer WR . tmc-1 encodes a sodium-sensitive channel required for salt chemosensation in C. elegans . Nature . 494 . 7435 . 95–99 . February 2013 . 23364694 . 4021456 . 10.1038/nature11845 . 2013Natur.494...95C . William Schafer (neuroscientist) .
  7. Liu J, Liu Y, Ren Y, Kang L, Zhang L . Transmembrane protein with unknown function 16A overexpression promotes glioma formation through the nuclear factor-κB signaling pathway . Molecular Medicine Reports . 9 . 3 . 1068–74 . March 2014 . 24401903 . 10.3892/mmr.2014.1888 . free .
  8. Web site: 1.A.17 The Calcium-Dependent Chloride Channel (Ca-ClC) Family. TCDB. 2016-04-16.
  9. Web site: Calcium activated chloride channel. IUPHAR/BPS Guide to Pharmacology. 7 October 2015.

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