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Pflugers Arch
2016 Oct 01;46810:1751-63. doi: 10.1007/s00424-016-1862-1.
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Relationship between TMEM16A/anoctamin 1 and LRRC8A.
Benedetto R, Sirianant L, Pankonien I, Wanitchakool P, Ousingsawat J, Cabrita I, Schreiber R, Amaral M, Kunzelmann K.
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TMEM16A/anoctamin 1/ANO1 and VRAC/LRRC8 are independent chloride channels activated either by increase in intracellular Ca(2+) or cell swelling, respectively. In previous studies, we observed overlapping properties for both types of channels. (i) TMEM16A/ANO1 and LRRC8 are inhibited by identical compounds, (ii) the volume-regulated anion channel VRAC requires compartmentalized Ca(2+) increase to be fully activated, (iii) anoctamins are activated by cell swelling, (iv) both channels have a role for apoptotic cell death, (v) both channels are possibly located in lipid rafts/caveolae like structures, and (vi) VRAC and anoctamin 1 currents are not additive when each are fully activated. In the present study, we demonstrate in different cell types that loss of LRRC8A expression not only inhibited VRAC, but also attenuated Ca(2+) activated Cl(-) currents. Moreover, expression of LRRC8A enhanced Ca(2+) activated Cl(-) currents, and both LRRC8A and ANO1 could be coimmunoprecipitated. We found that LRRC8A becomes accessible to biotinylation upon exposure to hypotonic bath solution, while membrane capacitance was not enhanced. When intracellular Ca(2+) was increased in ANO1-expressing cells, the membrane capacitance was enhanced and increased binding of FM4-64 to the membrane was observed. As this was not seen in cells lacking ANO1 expression, a role of ANO1 for exocytosis was suggested. We propose that ANO1 and LRRC8A are activated in parallel. Thus, ionomycin or purinergic stimulation will not only activate ANO1 but also LRRC8 currents. Cell swelling will not only activate LRRC8/VRAC, but also stimulate ANO1 currents by enhancing compartmentalized Ca(2+) increase and/or through swelling induced autocrine release of ATP.
Adinolfi,
P2X(7) receptor: Death or life?
2005, Pubmed
Adinolfi,
P2X(7) receptor: Death or life?
2005,
Pubmed Akita,
Regulation of bradykinin-induced activation of volume-sensitive outwardly rectifying anion channels by Ca2+ nanodomains in mouse astrocytes.
2011,
Pubmed Akita,
Ca2+ nanodomain-mediated component of swelling-induced volume-sensitive outwardly rectifying anion current triggered by autocrine action of ATP in mouse astrocytes.
2011,
Pubmed Almaça,
TMEM16 proteins produce volume-regulated chloride currents that are reduced in mice lacking TMEM16A.
2009,
Pubmed Boyd,
Determination of the levels of urokinase and its receptor in human colon carcinoma cell lines.
1988,
Pubmed Caputo,
TMEM16A, a membrane protein associated with calcium-dependent chloride channel activity.
2008,
Pubmed Courjaret,
Mid-range Ca2+ signalling mediated by functional coupling between store-operated Ca2+ entry and IP3-dependent Ca2+ release.
2014,
Pubmed
,
Xenbase De La Fuente,
Small-molecule screen identifies inhibitors of a human intestinal calcium-activated chloride channel.
2008,
Pubmed Depeursinge,
Digital holographic microscopy applied to life sciences.
2007,
Pubmed Gamper,
IGF-1 up-regulates K+ channels via PI3-kinase, PDK1 and SGK1.
2002,
Pubmed Hammer,
A Coding Variant of ANO10, Affecting Volume Regulation of Macrophages, Is Associated with Borrelia Seropositivity.
2015,
Pubmed
,
Xenbase Hartzell,
Activation of different Cl currents in Xenopus oocytes by Ca liberated from stores and by capacitative Ca influx.
1996,
Pubmed
,
Xenbase Hazama,
Biphasic rises in cytosolic free Ca2+ in association with activation of K+ and Cl- conductance during the regulatory volume decrease in cultured human epithelial cells.
1990,
Pubmed Hélix,
Inhibition of the endogenous volume-regulated anion channel (VRAC) in HEK293 cells by acidic di-aryl-ureas.
2003,
Pubmed Hoffmann,
Physiology of cell volume regulation in vertebrates.
2009,
Pubmed Jackson,
Single-channel properties of a volume-sensitive anion conductance. Current activation occurs by abrupt switching of closed channels to an open state.
1995,
Pubmed Jin,
Activation of the Cl- channel ANO1 by localized calcium signals in nociceptive sensory neurons requires coupling with the IP3 receptor.
2013,
Pubmed Juul,
Anoctamin 6 differs from VRAC and VSOAC but is involved in apoptosis and supports volume regulation in the presence of Ca2+.
2014,
Pubmed Kubitz,
Small-conductance chloride channels induced by cAMP, Ca2+, and hypotonicity in HT29 cells: ion selectivity, additivity and stilbene sensitivity.
1992,
Pubmed Kunzelmann,
Modulating Ca²⁺ signals: a common theme for TMEM16, Ist2, and TMC.
2016,
Pubmed Lariccia,
Massive calcium-activated endocytosis without involvement of classical endocytic proteins.
2011,
Pubmed Lemonnier,
Ca2+ modulation of volume-regulated anion channels: evidence for colocalization with store-operated channels.
2002,
Pubmed Martins,
Anoctamin 6 is an essential component of the outwardly rectifying chloride channel.
2011,
Pubmed McCarty,
Calcium signaling in cell volume regulation.
1992,
Pubmed Nilius,
Volume-activated Cl- channels.
1996,
Pubmed Nilius,
Properties of volume-regulated anion channels in mammalian cells.
1997,
Pubmed Okada,
Cell volume-sensitive chloride channels: phenotypic properties and molecular identity.
2006,
Pubmed Okada,
Volume-sensitive chloride channels involved in apoptotic volume decrease and cell death.
2006,
Pubmed Okada,
Volume expansion-sensing outward-rectifier Cl- channel: fresh start to the molecular identity and volume sensor.
1997,
Pubmed Ousingsawat,
Anoctamin 6 mediates effects essential for innate immunity downstream of P2X7 receptors in macrophages.
2015,
Pubmed
,
Xenbase Pedersen,
Biophysics and Physiology of the Volume-Regulated Anion Channel (VRAC)/Volume-Sensitive Outwardly Rectifying Anion Channel (VSOR).
2016,
Pubmed Pedersen,
Hypotonic cell swelling induces translocation of the alpha isoform of cytosolic phospholipase A2 but not the gamma isoform in Ehrlich ascites tumor cells.
2000,
Pubmed Pedersen,
Separate swelling- and Ca2+-activated anion currents in Ehrlich ascites tumor cells.
1998,
Pubmed Planells-Cases,
Subunit composition of VRAC channels determines substrate specificity and cellular resistance to Pt-based anti-cancer drugs.
2015,
Pubmed Qiu,
SWELL1, a plasma membrane protein, is an essential component of volume-regulated anion channel.
2014,
Pubmed Schroeder,
Expression cloning of TMEM16A as a calcium-activated chloride channel subunit.
2008,
Pubmed
,
Xenbase Sirianant,
Cellular volume regulation by anoctamin 6: Ca²⁺, phospholipase A2 and osmosensing.
2016,
Pubmed Sirianant,
Non-essential contribution of LRRC8A to volume regulation.
2016,
Pubmed Sørensen,
Dual role of LRRC8A-containing transporters on cisplatin resistance in human ovarian cancer cells.
2016,
Pubmed Sørensen,
Acquired cisplatin resistance in human ovarian A2780 cancer cells correlates with shift in taurine homeostasis and ability to volume regulate.
2014,
Pubmed Sørensen,
Downregulation of LRRC8A protects human ovarian and alveolar carcinoma cells against Cisplatin-induced expression of p53, MDM2, p21Waf1/Cip1, and Caspase-9/-3 activation.
2016,
Pubmed Strange,
Cellular and molecular physiology of volume-sensitive anion channels.
1996,
Pubmed Syeda,
LRRC8 Proteins Form Volume-Regulated Anion Channels that Sense Ionic Strength.
2016,
Pubmed Thoroed,
Cell swelling activates phospholipase A2 in Ehrlich ascites tumor cells.
1997,
Pubmed Trouet,
Caveolin-1 modulates the activity of the volume-regulated chloride channel.
1999,
Pubmed Trouet,
Inhibition of volume-regulated anion channels by dominant-negative caveolin-1.
2001,
Pubmed Voss,
Identification of LRRC8 heteromers as an essential component of the volume-regulated anion channel VRAC.
2014,
Pubmed Wu,
Biophysical characterization of styryl dye-membrane interactions.
2009,
Pubmed Yamamoto,
New molecular mechanisms for cardiovascular disease: cardiac hypertrophy and cell-volume regulation.
2011,
Pubmed Yang,
TMEM16A confers receptor-activated calcium-dependent chloride conductance.
2008,
Pubmed
,
Xenbase Yang,
Caveolin-1 mediates gene transfer and cytotoxicity of polyethyleneimine in mammalian cell lines.
2015,
Pubmed Yaradanakul,
Massive Ca-induced membrane fusion and phospholipid changes triggered by reverse Na/Ca exchange in BHK fibroblasts.
2008,
Pubmed Zeuthen,
Water transport by Na+-coupled cotransporters of glucose (SGLT1) and of iodide (NIS). The dependence of substrate size studied at high resolution.
2006,
Pubmed
,
Xenbase Zholos,
Ca(2+)- and volume-sensitive chloride currents are differentially regulated by agonists and store-operated Ca2+ entry.
2005,
Pubmed
