Anoctamin-1 | ANO-1 | TMEM -16A

Family:
Calcium-dependent chloride channels (Ca-CIC or CaCC family)

Members:
CaCCs that are known to occur in humans are encoded by the following genes:
Accessories: CLCA1 - CLCA4
Anoctamins: ANO-1 and ANO-2
Bestrophins: BEST1 - BEST4

Topology:
CaCC channels are a 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, including proteins from several structurally different families: chloride channel accessory (CLCA), bestrophin (BEST), and calcium-dependent chloride channel anoctamin (ANO or TMEM16) channels. Members of the Ca-CIC family exhibit 7 to 10 transmembrane segments.

Background Information ANO-1

Anoctamin-1 (ANO1), also known as Transmembrane member 16A (TMEM16A), functions as a calcium-activated chloride channel. Ca2+, Sr2+, and Ba2+ activate the channel in smooth muscle and epithelial cells. ATP and calmodulin are essential for its activation. Channel activity is inhibited by CFTR protein and by chloride inhibitors such as niflumic acid (NFA) and 4,4'-diisothiocyanatostilbene-2,2'-disulfonic acid (DIDS). ANO1 is essential for chloride secretion from epithelial tissues, and has been shown to be a specific marker for cells of Cajal, the pacemaker cells that control smooth muscle contraction. Anoctamin 1 knockout mice exhibit an altered gastric smooth muscle rhythmic contraction. Research studies have identified Anoctamin 1 as a heat sensor in nociceptive neurons. Heat above 44ºC triggers anoctamin 1-dependent depolarization, contributing to the mediation of thermal nociception.

Gene:
ANO1

Human Protein:
UniProt Q5XXA6

Tissue:
ANO-1 is found in smooth muscle and epithelial cells. It is broadly expressed with higher levels in liver, skeletal muscle and gastrointestinal muscles, especially in human interstitial cells of Cajal (ICC) throughout the gastrointestinal tract. Furthermore, Ano-1 is found in nociceptice neurons.

Function/ Application:
Transepithelial anion transport and smooth muscle contraction. Required for the normal functioning of the interstitial cells of Cajal (ICCs) which generate electrical pacemaker activity in gastrointestinal smooth muscles. Acts as a major contributor to basal and stimulated chloride conductance in airway epithelial cells and plays an important role in tracheal cartilage development.

Pathology:
Frontal Sinus Squamous Cell Carcinoma, Liver Leiomyoma, multiple myeloma, breast carcinoma, oral cancer, gastrointestinal stromal tumor, frontal sinus cancer

Interaction:
Ezrin, radixin, moesin, RhoA, VAMP3, syntaxins 2 and -4, and syntaxin-binding proteins munc18b and munc18c

Modulator:
Niflumic acid (NFA), carbachol, crofelemer, 4,4'-diisothiocyanatostilbene-2,2'-disulfonic acid (DIDS), tannic acid, fluoxetine, flufenamic acid, talniflumate

Assays:
Patch Clamp: whole cell, intracellular solution exchange, temperatur control

Recommended Reviews:
Huang E., Wong X., Jan L.Y. (2012) International Union of Basic and Clinical Pharmacology. LXXXV: calcium-activated chloride channels. Pharmacol Rev 64(1):1-15

Application Notes

TMEM16A (ANO1) - "Internal perfusion of Ca2+ to activate TMEM16A/ANO1 on the SyncroPatch 384PE"

icon sp96   SyncroPatch 384PE (a predecessor model of SyncroPatch 384i) application note   logo pdf   (1.1 MB)
Cells were kindly provided by SB Drug Discovery.

Posters

2017 - lnvestigation of the Ion Channels hTMEM16A/Ano1 and TRPC5 and their Modulation by Intracellular Calcium

icon sp96   SyncroPatch 384PE (a predecessor model of SyncroPatch 384i) poster, BPS Meeting 2017  logo pdf   (1.3 MB)

Publications

2018 - Towards Novel Bioactive Antiperspirants for Cosmetic Applications

icon sp96   SyncroPatch 384PE (a predecessor model of SyncroPatch 384i) publication in IFSCC (2018)

Authors:
Ertongur-Fauth T., Fischer S., Hartmann D., Brüggemann A., Seeger V., Kleber A., Krohn M.

 

 

Cookies make it easier for us to provide you with our services. With the usage of our services you permit us to use cookies.