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 Na+, K+, Ca2+, and/or Cl− to pass through the membrane in res ...

s for

chloride The chloride ion is the anion (negatively charged ion) Cl−. It is formed when the element chlorine (a halogen) gains an electron or when a compound such as hydrogen chloride is dissolved in water or other polar solvents. Chloride s ...

that have been identified in many

epithelial Epithelium or epithelial tissue is one of the four basic types of animal tissue, along with connective tissue, muscle tissue and nervous tissue. It is a thin, continuous, protective layer of compactly packed cells with a little intercellu ...

and

endothelial cell The endothelium 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 the rest of the vesse ...

types as well as in

smooth muscle cell Smooth muscle is an involuntary non-striated muscle, so-called because it has no sarcomeres and therefore no striations (''bands'' or ''stripes''). It is divided into two subgroups, single-unit and multiunit smooth muscle. Within single-unit mus ...

s. 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 Anoctamin-1 (ANO1) also known as Transmembrane member 16A (TMEM16A) is a protein that, in humans, is encoded by the ''ANO1'' gene. Anoctamin-1 is a voltage-gated calcium-activated anion channel, which acts as a chloride channel and a bicarbonate ...

is highly expressed in human gastrointestinal

interstitial cells of Cajal Interstitial cells of Cajal (ICC) are interstitial cells found in the gastrointestinal tract. There are different types of ICC with different functions. ICC and another type of interstitial cell, known as platelet-derived growth factor receptor ...

, which are proteins which serve as intestinal pacemakers for

peristalsis Peristalsis ( , ) is a radially symmetrical contraction and relaxation of muscles that propagate in a wave down a tube, in an anterograde direction. Peristalsis is progression of coordinated contraction of involuntary circular muscles, whi ...

. 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. 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 tissue, and persists ...

suppressor A silencer, also known as a sound suppressor, suppressor, or sound moderator, is a muzzle device that reduces the acoustic intensity of the muzzle report (sound of a gunshot) and muzzle rise when a gun (firearm or air gun) is discharged, b ...

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'' () is a genus of flies, belonging to the family Drosophilidae, whose members are often called "small fruit flies" or (less frequently) pomace flies, vinegar flies, or wine flies, a reference to the characteristic of many speci ...

'' and 2 in ''

C. elegans ''Caenorhabditis elegans'' () is a free-living transparent nematode about 1 mm in length that lives in temperate soil environments. It is the type species of its genus. The name is a blend of the Greek ''caeno-'' (recent), ''rhabditis'' (r ...

''. One of the latter two is expressed in mechanoreceptors. Tmc1 is a sodium-sensitive cation channel required for salt (Na⁺) chemosensation in ''

'' "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:

and ANO2 (potentially others) *Bestrophins:

BEST1 Bestrophin-1 (Best1) is a protein that, in humans, is encoded by the ''BEST1'' gene (RPD ID - 5T5N/4RDQ). The bestrophin family of proteins comprises four evolutionary related genes (BEST1, BEST2, BEST3, and BEST4) that code for integral membrane ...

BEST2 Bestrophin-2 is a protein that in humans is encoded by the ''BEST2'' gene In biology, the word gene (from , ; "...Wilhelm Johannsen coined the word gene to describe the Mendelian units of heredity..." meaning ''generation'' or ''birth'' o ...

, BEST3, and BEST4

Function

In humans

See also

Notes

References

Further reading