Anoctamin-1 (ANO1) also known as Transmembrane member 16A (TMEM16A) is a
protein
Proteins are large biomolecules and macromolecules that comprise one or more long chains of amino acid residues. Proteins perform a vast array of functions within organisms, including catalysing metabolic reactions, DNA replication, respo ...
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
Chloride channels are a superfamily of poorly understood ion channels specific for chloride. These channels may conduct many different ions, but are named for chloride because its concentration ''in vivo'' is much higher than other anions. Severa ...
and a bicarbonate channel. additionally Anoctamin-1 is apical iodide channel.
It is expressed in smooth muscle, epithelial cells,
, olfactory
sustentacular cell
A sustentacular cell is a type of cell primarily associated with structural support, they can be found in various tissues.
* Sustentacular cells of the olfactory epithelium (also called supporting cells) have been shown to be involved in the phag ...
s, and is highly expressed in
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 ...
(ICC) throughout the
gastrointestinal tract
The gastrointestinal tract (GI tract, digestive tract, alimentary canal) is the tract or passageway of the digestive system that leads from the mouth to the anus. The GI tract contains all the major organ (biology), organs of the digestive syste ...
.
Function
ANO1 is a transmembrane protein that functions as a
calcium-activated chloride channel
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 a ...
.
,
Sr2+, and
Ba2+ activate the channel.
Structure
No atomic resolution structure of this channel has yet been obtained. However, biochemical evidence suggests that the channel assembles as a dimer of two ANO1 polypeptide subunits.
From hydropathy plotting, each subunit is thought to encode a molecule with eight transmembrane domains, with a reentrant loop between the fifth and sixth transmembrane domains. The reentrant loop is thought to be a
P loop
P, or p, is the sixteenth letter (alphabet), letter of the Latin alphabet, used in the English alphabet, modern English alphabet, the alphabets of other western European languages and others worldwide. Its name in English is English alphabet#L ...
-like structure responsible for the ion selectivity of the protein.
Clinical significance
In mice, the functional expression of the ANO1 channel is essential to life, as its absence leads to a premature death due to respiratory collapse.
ANO1 is expressed in the gastrointestinal tract and is highly expressed in interstitial cells of Cajal, where it plays an important role in pacemaker activity, neurotransduction of enteric motor neurotransmitters and regulation of
gastrointestinal motility Gastrointestinal physiology is the branch of human physiology that addresses the physical function of the gastrointestinal (GI) tract. The function of the GI tract is to process ingested food by mechanical and chemical means, extract nutrients and ...
.
ANO1 blockers like
niflumic acid
Niflumic acid is a drug used for joint and muscular pain. It is categorized as an inhibitor of cyclooxygenase-2. In experimental biology, it has been employed to inhibit chloride channel
Chloride channels are a superfamily of poorly understood ...
have been shown to block
slow waves, which produce phasic contractions and the major patterns of gastrointestinal motility, such as peristalsis and segmentation.
ANO1-knockout mice fail to produce slow waves altogether.
Carbachol
Carbachol, also known as carbamylcholine and sold under the brand name Miostat among others, is a cholinomimetic drug that binds and activates acetylcholine receptors. Thus it is classified as a cholinergic agonist. It is primarily used for var ...
has been shown to markedly activate the channel due to its effect on release of Ca2+ from intracellular stores.
ANO1 activation is necessary for normal function of ICC and generation of normal patterns of activity in smooth muscles of the gastrointestinal tract.
Its overexpression was reported in
esophageal squamous cell carcinoma
Esophageal cancer is cancer arising from the esophagus—the food pipe that runs between the throat and the stomach. Symptoms often include difficulty in swallowing and weight loss. Other symptoms may include pain when swallowing, a hoarse voi ...
and breast cancer progression.
References
Further reading
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External links
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{{Ion channels, g4
Chloride channels