Anoctamins

Kunzelmann, Karl; Tian, Yuemin; Martins, Joana Raquel; Faria, Diana; Kongsuphol, Patthara; Ousingsawat, Jiraporn; Thévenod, Frank; Roussa, Eleni; Rock, Jason R.; Schreiber, Rainer

doi:10.1007/s00424-011-0975-9

Cited by 104 publications

(103 citation statements)

References 121 publications

(186 reference statements)

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“…To that end we coexpressed different anoctamins together with P2Y 2 receptors in HEK293 cells, which were stimulated by 10 mM ATP, in the presence of a cytosol-like pipette filling solution and extracellular Ringer solution (see the Materials and Methods). We observed that overexpressed Ano1 and Ano6 produce significant whole-cell Cl 2 currents, even in the absence of ATP stimulation (Kunzelmann et al, 2011b). In cells expressing Ano1,4,7,8,9 and 10, whole-cell currents of variable magnitudes were activated by ATP (Fig.…”

Section: Resultsmentioning

confidence: 65%

Anoctamins are a family of Ca2+ activated Cl− channels

Tian

Schreiber

Kunzelmann

2012

Journal of Cell Science

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SummaryAnoctamin 1 (Ano1; TMEM16A) and anoctamin 2 (Ano2; TMEM16B) are novel Cl 2 channels transiently activated by an increase in intracellular Ca 2+. These channels are essential for epithelial Cl 2 secretion, smooth muscle peristalsis and olfactory signal transduction. They are central to inherited diseases and cancer and can act as heat sensors. Surprisingly, another member of this protein family, Ano6, operates as a Ca 2+ -activated phospholipid scramblase, and others were reported as intracellular proteins. It is therefore unclear whether anoctamins constitute a family of Ca 2+ -activated Cl 2 channels, or are proteins with heterogeneous functions. Using whole-cell patch clamping we demonstrate that Ano4-10 are all able to produce transient Ca 2+ -activated Cl 2 currents when expressed in HEK293 cells. Although some anoctamins (Ano1, 2, 4, 6, 7) were found to be well expressed in the plasma membrane, others (Ano8, 9, 10) show rather poor membrane expression and were mostly retained in the cytosol. The transient nature of the Cl 2 currents was demonstrated to be independent of intracellular Ca 2+ levels. We show that inactivation of Ano1 currents occurs in the continuous presence of elevated Ca 2+ concentrations, possibly by calmodulin-dependent kinase. The present results demonstrate that anoctamins are a family of Ca 2+ -activated Cl 2 channels, which also induce permeability for cations. They may operate as Cl 2 channels located in the plasma membrane or in intracellular compartments. These results increase our understanding of the physiological significance of anoctamins and their role in disease.

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Section: Resultsmentioning

confidence: 65%

Anoctamins are a family of Ca2+ activated Cl− channels

Tian

Schreiber

Kunzelmann

2012

Journal of Cell Science

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161

176

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“…The relationship between ion channel currents, cell volume regulation, migration and metastasis is well established [30][31][32][33]. Previous findings indicate that Ano1 is activated during hypotonic cell swelling and contributes to regulatory volume decrease (RVD), which certainly requires a rise in intracellular Ca 2þ [5,27,34]. A rise in intracellular Ca 2þ may activate Ano1 together with K þ channels to release intracellular K þ and Cl 2 ions.…”

Section: Role Of Ano1 For Metastasismentioning

confidence: 99%

Role of anoctamins in cancer and apoptosis

Wanitchakool

Wolf

Koehl

et al. 2014

Phil. Trans. R. Soc. B

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Anoctamin 1 (TMEM16A, Ano1) is a recently identified Ca 2+ -activated chloride channel and a member of a large protein family comprising 10 paralogues. Before Ano1 was identified as a chloride channel protein, it was known as the cancer marker DOG1. DOG1/Ano1 is expressed in gastrointestinal stromal tumours (GIST) and particularly in head and neck squamous cell carcinoma, at very high levels never detected in other tissues. It is now emerging that Ano1 is part of the 11q13 locus, amplified in several types of tumour, where it is thought to augment cell proliferation, cell migration and metastasis. Notably, Ano1 is upregulated through histone deacetylase (HDAC), corresponding to the known role of HDAC in HNSCC. As Ano1 does not enhance proliferation in every cell type, its function is perhaps modulated by cell-specific factors, or by the abundance of other anoctamins. Thus Ano6, by regulating Ca 2+ -induced membrane phospholipid scrambling and annexin V binding, supports cellular apoptosis rather than proliferation. Current findings implicate other cellular functions of anoctamins, apart from their role as Ca 2+ -activated Cl − channels.

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“…An additional suggestion for close association between Ca 2+ release sites and ANO1–CaCCs came from oocyte recordings: in oocytes overexpressing ANO1 and P2Y 2 receptors, whole‐cell currents activated by the Ca 2+ ionophore ionomycin displayed an outward rectification, while ATP‐activated currents had linear current–voltage relationships, suggesting higher local Ca 2+ concentrations near ANO1 channels in the latter case (Kunzelmann et al . 2011, 2012). …”

Section: Coupling Between Ano1 and Endoplasmic Reticulum; Is This A Gmentioning

confidence: 99%

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

Jin

Shah

et al. 2014

The Journal of Physiology

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Ca2+‐activated chloride channels (CaCCs) regulate numerous physiological processes including epithelial transport, smooth muscle contraction and sensory processing. Anoctamin‐1 (ANO1, TMEM16A) is a principal CaCC subunit in many cell types, yet our understanding of the mechanisms of ANO1 activation and regulation are only beginning to emerge. Ca2+ sensitivity of ANO1 is rather low and at negative membrane potentials the channel requires several micromoles of intracellular Ca2+ for activation. However, global Ca2+ levels in cells rarely reach such levels and, therefore, there must be mechanisms that focus intracellular Ca2+ transients towards the ANO1 channels. Recent findings indeed indicate that ANO1 channels often co‐localize with sources of intracellular Ca2+ signals. Interestingly, it appears that in many cell types ANO1 is particularly tightly coupled to the Ca2+ release sites of the intracellular Ca2+ stores. Such preferential coupling may represent a general mechanism of ANO1 activation in native tissues.

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Anoctamins

Cited by 104 publications

References 121 publications

Anoctamins are a family of Ca2+ activated Cl− channels

Anoctamins are a family of Ca2+ activated Cl− channels

Role of anoctamins in cancer and apoptosis

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

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Anoctamins

Cited by 104 publications

References 121 publications

Anoctamins are a family of Ca2+ activated Cl− channels

Anoctamins are a family of Ca2+ activated Cl− channels

Role of anoctamins in cancer and apoptosis

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

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