The Calcium-Dependent Chloride Channel (Ca-ClC) proteins (or calcium-activated chloride channels (CaCCs), are heterogeneous groups of

ligand-gated ion channel Ligand-gated ion channels (LICs, LGIC), also commonly referred to as ionotropic receptors, are a group of transmembrane ion-channel proteins which open to allow ions such as sodium, Na+, potassium, K+, calcium, Ca2+, and/or chloride, Cl− to ...

s for

chloride The term chloride refers to a compound or molecule that contains either a chlorine anion (), which is a negatively charged chlorine atom, or a non-charged chlorine atom covalently bonded to the rest of the molecule by a single bond (). The pr ...

that have been identified in many

epithelial Epithelium or epithelial tissue is a thin, continuous, protective layer of cells with little extracellular matrix. An example is the epidermis, the outermost layer of the skin. Epithelial ( mesothelial) tissues line the outer surfaces of man ...

and

endothelial cell The endothelium (: endothelia) is a single layer of squamous endothelial cells that line the interior surface of blood vessels and lymphatic vessels. The endothelium forms an interface between circulating blood or lymph in the lumen and th ...

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 Peristalsis ( , ) is a type of intestinal motility, characterized by symmetry in biology#Radial symmetry, radially symmetrical contraction and relaxation of muscles that propagate in a wave down a tube, in an wikt:anterograde, anterograde dir ...

. In addition to their role as chloride channels some CLCA proteins function as adhesion molecules and may also have roles as

tumour A neoplasm () is a type of abnormal and excessive growth of tissue (biology), tissue. The process that occurs to form or produce a neoplasm is called neoplasia. The growth of a neoplasm is uncoordinated with that of the normal surrounding tiss ...

suppressor A silencer, also known as a sound suppressor, suppressor, or sound moderator, is a gun barrel#Muzzle, muzzle device that suppresses the muzzle blast, blast created when a gun (firearm or airgun) is discharged, thereby reducing the sound inten ...

s. These eukaryotic proteins are "required for normal electrolyte and fluid secretion, olfactory perception, and neuronal and smooth muscle excitability" in animals. 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
an
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 famil
TC# 1.A.82
. Mice lacking both channels lack hair cell mechanosensory potentials. There are 8 members of this family in humans, 1 in ''

Drosophila ''Drosophila'' (), from Ancient Greek δρόσος (''drósos''), meaning "dew", and φίλος (''phílos''), meaning "loving", is a genus of fly, belonging to the family Drosophilidae, whose members are often called "small fruit flies" or p ...

'' and 2 in '' C. elegans''. One of the latter two is expressed in mechanoreceptors. 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". 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. The reactions believed to be catalyzed by channels of the Ca-ClC family are:

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: *Accessories: CLCA1, CLCA2, CLCA3, and CLCA4 *Anoctamins: ANO1 and ANO2 (potentially others) *Bestrophins: BEST1, BEST2, BEST3, and BEST4

Function

In humans

See also

Notes

References

Further reading