Ano1 is a selective marker of interstitial cells of Cajal in the human and mouse gastrointestinal tract

Abstract

Populations of interstitial cells of Cajal (ICC) are altered in several gastrointestinal neuromuscular disorders. ICC are identified typically by ultrastructure and expression of Kit (CD117), a protein that is also expressed on mast cells. No other molecular marker currently exists to independently identify ICC. The expression of ANO1 (DOG1, TMEM16A), a Ca(2+)-activated Cl(-) channel, in gastrointestinal stromal tumors suggests it may be useful as an ICC marker. The aims of this study were therefore to determine the distribution of Ano1 immunoreactivity compared with Kit and to establish whether Ano1 is a reliable marker for human and mouse ICC. Expression of Ano1 in human and mouse stomach, small intestine, and colon was investigated by immunofluorescence labeling using antibodies to Ano1 alone and in combination with antibodies to Kit. Colocalization of immunoreactivity was demonstrated by epifluorescence and confocal microscopy. In the muscularis propria, Ano1 immunoreactivity was restricted to cells with the morphology and distribution of ICC. All Ano1-positive cells in the muscularis propria were also Kit positive. Kit-expressing mast cells were not Ano1 positive. Some non-ICC in the mucosa and submucosa of human tissues were Ano1 positive but Kit negative. A few (3.2%) Ano1-positive cells in the human gastric muscularis propria were labeled weakly for Kit. Ano1 labels all classes of ICC and represents a highly specific marker for studying the distribution of ICC in mouse and human tissues with an advantage over Kit since it does not label mast cells.

Activation of Ca2+‐activated Cl− channel ANO1 by localized Ca2+ signals

“…ANO1 is robustly expressed in ICCs (Gomez‐Pinilla et al . 2009); moreover, electrical activity and contractility in the gastrointestinal tract have been severely compromised in ANO1 knockout mice (Huang et al . 2009; Hwang et al .…”

Role of anoctamins in cancer and apoptosis

“…Expression of DOG1 correlates with poor outcome in oesophageal squamous cell cancer [10][11][12]. Interstitial cells of Cajal (ICC) are another predominant site for Ano1 expression [13][14][15]. It has been reported that mice lacking Ano1 had fewer proliferating ICC [16].…”

The Role of Waixenicin A as Transient Receptor Potential Melastatin 7 Blocker

“…2E). Recently, Zhu et al [13] suggested that Ca 2+ -activated Cl À conductance is involved in the pacemaking activity of ICCs, and another recent study confirmed that ICCs express ANO1 in the GI tract [14]. In addition, ANO1 was recently shown to function as a Ca 2+ -activated Cl À channel [15][16][17], and loss or block of ANO1 was found to block electrical slow waves in intact GI muscles [18].…”