Expression and Function of Epithelial Anoctamins

Schreiber, Rainer; Uliyakina, Inna; Kongsuphol, Patthara; Warth, Richard; Mirza, Myriam; Martins, Joana Raquel; Kunzelmann, Karl

doi:10.1074/jbc.m109.065367

Cited by 203 publications

(256 citation statements)

References 28 publications

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“…Many studies report ORCC in epithelial cells (1)(2)(3)18), which corresponds well to the broad expression of Ano6 in all epithelial tissues and cell lines analyzed here and in a previous report (15) (Fig. 3 A and B).…”

Section: Resultssupporting

confidence: 91%

“…Homodimerization has been shown meanwhile for Ano1 (24,25). Although heterooligomerization has not yet been detected, we speculate that Ano6 may form variable oligomeric protein complexes in different cell types, thereby shaping ORCC in different cell types (15). Moreover, association with accessory proteins is possible and should be examined in the future.…”

Section: Resultsmentioning

confidence: 83%

“…Anoctamins (TMEM16) have been identified as a family of putative Cl − channels, with Ano1 (TMEM16A) being an essential component of the long unknown Ca 2+ -activated Cl − channel (12)(13)(14). Other anoctamins, such as anoctamin (Ano6), do not seem to produce fast Ca 2+ -gated Cl − channels (15). Because both anoctamins and ORCC are found in most if not all cell types, and because Ano1 and ORCC have a similar halide permeability and are both inhibited by the same blockers such 4,4′-diisothiocyanostilbene-2,2′-disulfonic acid (DIDS) or 5-nitro-2-(3-phenylpropylamino) benzoic acid (NPPB), we asked whether ORCC is formed by a member of the anoctamin family.…”

mentioning

confidence: 99%

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Anoctamin 6 is an essential component of the outwardly rectifying chloride channel

Martins

Faria

Kongsuphol

et al. 2011

Proc. Natl. Acad. Sci. U.S.A.

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Outwardly rectifying chloride channels (ORCC, ICOR) of intermediate single-channel conductance of around 50 pS, are ubiquitously expressed, but have remained a mystery since their description more than 25 y ago. These channels have been shown to be activated on membrane excision and depolarization of the membrane voltage and by cAMP in the presence of the cystic fibrosis transmembrane conductance regulator. We show that anoctamin 6 (Ano6), a member of the recently identified family of putative Cl − channels, is the crucial component of ORCC single-channel and whole-cell currents in airway epithelial cells and Jurkat T lymphocytes. Cystic fibrosis transmembrane conductance regulator augmented ORCC produced by Ano6 in A549 airway epithelial cells. Ano6 is activated during membrane depolarization or apoptosis of Jurkat T lymphocytes and epithelial cells, and is inhibited by 5-nitro-2-(3-phenylpropylamino) benzoic acid, 4,4′-diisothio-cyanostilbene-2,2′-disulfonic acid, or AO1. Ano6 belongs to the basic equipment of any cell type, including colonic surface epithelial cells. It forms the essential component of ORCC and seems to have a role for cell shrinkage and programmed cell death.

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Section: Resultssupporting

confidence: 91%

Section: Resultsmentioning

confidence: 83%

mentioning

confidence: 99%

See 1 more Smart Citation

Anoctamin 6 is an essential component of the outwardly rectifying chloride channel

Martins

Faria

Kongsuphol

et al. 2011

Proc. Natl. Acad. Sci. U.S.A.

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140

161

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“…3). These results are consistent with the finding of Schreiber et al (23), which demonstrates plasma membrane expression of most ANOs, including ANO6 in HEK293 cells. To conclude this section, our data provide evidence that ANO6 constitutes a Ca 2ϩ -activated Cl Ϫ channel (because A23187 was activated) and express in the plasma membrane that was activated by Ace in a calcium-independent mechanism.…”

Section: Discussionsupporting

confidence: 93%

“…The ANO protein family consists of 10 members with tissuespecific patterns of expression (23). To explore whether and which isoforms of the ANO channels were expressed in intestinal epithelia and could contribute to or be accounted for the Ace-induced chloride conductance, qPCR analysis was performed with primers specific for ANO1 and ANO6 genes.…”

Section: Apical Challenge Of Recombinant Ace Protein Induced a Rapid mentioning

confidence: 99%

Anoctamin 6 Contributes to Cl− Secretion in Accessory Cholera Enterotoxin (Ace)-stimulated Diarrhea

Aoun

Hayashi

Sheikh

et al. 2016

Journal of Biological Chemistry

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Edited by F. Anne StephensonAccessory cholera enterotoxin (Ace) of Vibrio cholerae has been shown to contribute to diarrhea. However, the signaling mechanism and specific type of Cl ؊ channel activated by Ace are still unknown. We have shown here that the recombinant Ace protein induced I Cl of apical plasma membrane, which was inhibited by classical CaCC blockers. Surprisingly, an Ace-elicited rise of current was neither affected by ANO1 (TMEM16A)-specific inhibitor T16A (inh) -AO1(TAO1) nor by the cystic fibrosis transmembrane conductance regulator (CFTR) blocker, CFTR inh-172. Ace stimulated whole-cell current in Caco-2 cells. However, the apical I Cl was attenuated by knockdown of ANO6 (TMEM16F). This impaired phenotype was restored by

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