A Coding Variant of ANO10, Affecting Volume Regulation of Macrophages, Is Associated with Borrelia Seropositivity

Hammer, Christian; Wanitchakool, Podchanart; Sirianant, Lalida; Papiol, Sergi; Monnheimer, Mathieu; Faria, Diana; Ousingsawat, Jiraporn; Schramek, Natalie; Schmitt, Corinna; Margos, Gabriele; Michel, Angelika; Kraiczy, Peter; Pawlita, Michael; Schreiber, Rainer; Schulz, Thomas F.; Fingerle, Volker; Tumani, Hayrettin; Ehrenreich, Hannelore; Kunzelmann, Karl

doi:10.2119/molmed.2014.00219

Cited by 49 publications

(52 citation statements)

References 53 publications

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“…Notably, we also found higher caspase 3/7 activity in cells expressing ANO10, and even more remarkably, coexpression of both LRRC8A and ANO10 potentiated caspase activity. These results confirm the roles of LRRC8A and ANO10 in apoptotic cell death and support the notion of a functional interaction of LRRC8A and ANO10 (Hammer et al 2015). We found earlier that ANO10 induces VRAC when expressed in oocytes from X. laevis, while the variant R263H fails to induce VRAC (Hammer et al 2015).…”

Section: Volume Regulation and Apoptosis By Lrrc8a And Ano10supporting

confidence: 90%

“…These results confirm the roles of LRRC8A and ANO10 in apoptotic cell death and support the notion of a functional interaction of LRRC8A and ANO10 (Hammer et al 2015). We found earlier that ANO10 induces VRAC when expressed in oocytes from X. laevis, while the variant R263H fails to induce VRAC (Hammer et al 2015). Notably, expression of LRRC8A also induced VRAC in Xenopus oocytes, which is very different from mammalian cells, where overexpression of LRRC8A did not generate additional VRAC (Qiu et al 2014;Voss et al 2014).…”

Section: Volume Regulation and Apoptosis By Lrrc8a And Ano10supporting

confidence: 88%

“…Coimmunoprecipitation and Western blotting of ANO6, ANO9, CFTR, and LRRC8A were performed as described earlier (Hammer et al 2015;Sirianant et al 2015). Proteins were separated by 8.5 % sodium dodecyl sulfate (SDS) polyacrylamide gel electrophoresis (PAGE) and transferred to a polyvinyl membrane (GE Healthcare, Munich, Germany).…”

Section: Coimmunoprecipitation and Western Blottingmentioning

confidence: 99%

“…Notably, expression of LRRC8A also induced VRAC in Xenopus oocytes, which is very different from mammalian cells, where overexpression of LRRC8A did not generate additional VRAC (Qiu et al 2014;Voss et al 2014). Evidence is provided that ANO10 controls compartmentalized Ca 2+ signaling, which possibly may control VRAC activity (Hammer et al 2015;Sirianant et al 2015). It was suggested that attenuated VRAC function in macrophages expressing one copy of R263H interferes with their phagocytic activity.…”

Section: Volume Regulation and Apoptosis By Lrrc8a And Ano10mentioning

confidence: 99%

“…It was suggested that attenuated VRAC function in macrophages expressing one copy of R263H interferes with their phagocytic activity. Thus, reduced clearance of Borrelia by macrophages may lead to enhanced Borrelia antibody titers detected in carriers of the R263H variant (Hammer et al 2015). At any rate, the impact of LRRC8/ VRAC on apoptosis appears to be cell dependent.…”

Section: Volume Regulation and Apoptosis By Lrrc8a And Ano10mentioning

confidence: 99%

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Cl− channels in apoptosis

et al. 2016

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A remarkable feature of apoptosis is the initial massive cell shrinkage, which requires opening of ion channels to allow release of K, Cl, and organic osmolytes to drive osmotic water movement and cell shrinkage. This article focuses on the role of the Cl channels LRRC8, TMEM16/anoctamin, and cystic fibrosis transmembrane conductance regulator (CFTR) in cellular apoptosis. LRRC8A-E has been identified as a volume-regulated anion channel expressed in many cell types. It was shown to be required for regulatory and apoptotic volume decrease (RVD, AVD) in cultured cell lines. Its presence also determines sensitivity towards cytostatic drugs such as cisplatin. Recent data point to a molecular and functional relationship of LRRC8A and anoctamins (ANOs). ANO6, 9, and 10 (TMEM16F, J, and K) augment apoptotic Cl currents and AVD, but it remains unclear whether these anoctamins operate as Cl channels or as regulators of other apoptotic Cl channels, such as LRRC8. CFTR has been known for its proapoptotic effects for some time, and this effect may be based on glutathione release from the cell and increase in cytosolic reactive oxygen species (ROS). Although we find that CFTR is activated by cell swelling, it is possible that CFTR serves RVD/AVD through accumulation of ROS and activation of independent membrane channels such as ANO6. Thus activation of ANO6 will support cell shrinkage and induce additional apoptotic events, such as membrane phospholipid scrambling.

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Section: Volume Regulation and Apoptosis By Lrrc8a And Ano10supporting

confidence: 90%

Section: Volume Regulation and Apoptosis By Lrrc8a And Ano10supporting

confidence: 88%

Section: Coimmunoprecipitation and Western Blottingmentioning

confidence: 99%

Section: Volume Regulation and Apoptosis By Lrrc8a And Ano10mentioning

confidence: 99%

Section: Volume Regulation and Apoptosis By Lrrc8a And Ano10mentioning

confidence: 99%

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Cl− channels in apoptosis

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Molecular, biophysical, and pharmacological properties of calcium‐activated chloride channels

Kamaleddin

2017

Journal Cellular Physiology

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Calcium-activated chloride channels (CaCCs) are a family of anionic transmembrane ion channels. They are mainly responsible for the movement of Cl and other anions across the biological membranes, and they are widely expressed in different tissues. Since the Cl flow into or out of the cell plays a crucial role in hyperpolarizing or depolarizing the cells, respectively, the impact of intracellular Ca concentration on these channels is attracting a lot of attentions. After summarizing the molecular, biophysical, and pharmacological properties of CaCCs, the role of CaCCs in normal cellular functions will be discussed, and I will emphasize how dysregulation of CaCCs in pathological conditions can account for different diseases. A better understanding of CaCCs and a pivotal regulatory role of Ca can shed more light on the therapeutic strategies for different neurological disorders that arise from chloride dysregulation, such as asthma, cystic fibrosis, and neuropathic pain.

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Ion channels in regulated cell death

Kunzelmann

2016

Cell. Mol. Life Sci.

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Activation of ion channels and pores are essential steps during regulated cell death. Channels and pores participate in execution of apoptosis, necroptosis and other forms of caspase-independent cell death. Within the program of regulated cell death, these channels are strategically located. Ion channels can shrink cells and drive them towards apoptosis, resulting in silent, i.e. immunologically unrecognized cell death. Alternatively, activation of channels can induce cell swelling, disintegration of the cell membrane, and highly immunogenic necrotic cell death. The underlying cell death pathways are not strictly separated as identical stimuli may induce cell shrinkage and apoptosis when applied at low strength, but may also cause cell swelling at pronounced stimulation, resulting in regulated necrosis. Nevertheless, the precise role of ion channels during regulated cell death is far from being understood, as identical channels may support regulated death in some cell types, but may cause cell proliferation, cancer development, and metastasis in others. Along this line, the phospholipid scramblase and Cl(-)/nonselective channel anoctamin 6 (ANO6) shows interesting features, as it participates in apoptotic cell death during lower levels of activation, thereby inducing cell shrinkage. At strong activation, e.g. by stimulation of purinergic P2Y7 receptors, it participates in pore formation, causes massive membrane blebbing, cell swelling, and membrane disintegration. The LRRC8 proteins deserve much attention as they were found to have a major role in volume regulation, apoptotic cell shrinkage and resistance towards anticancer drugs.

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A Coding Variant of ANO10, Affecting Volume Regulation of Macrophages, Is Associated with Borrelia Seropositivity

Cited by 49 publications

References 53 publications

Cl− channels in apoptosis

Cl− channels in apoptosis

Molecular, biophysical, and pharmacological properties of calcium‐activated chloride channels

Ion channels in regulated cell death

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