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Pflugers Arch
2015 Oct 01;46710:2121-40. doi: 10.1007/s00424-015-1687-3.
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Homodimeric anoctamin-1, but not homodimeric anoctamin-6, is activated by calcium increases mediated by the P2Y1 and P2X7 receptors.
Stolz M, Klapperstück M, Kendzierski T, Detro-Dassen S, Panning A, Schmalzing G, Markwardt F.
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The P2X7 receptor (P2X7R) is a ligand-gated ion channel that conducts Na(+), K(+), and Ca(2+) when activated by extracellular ATP. In various cell types, such as secretory epithelia, the P2X7R is co-expressed with Ca(2+)-dependent Cl(-) channels of the TMEM16/anoctamin family. Here, we studied whether the P2X7R and TMEM16A/anoctamin-1 (Ano1) or TMEM16F/anoctamin-6 (Ano6) interact functionally and physically, using oocytes of Xenopus laevis and Ambystoma mexicanum (Axolotl) for heterologous expression. As a control, we co-expressed anoctamin-1 with the P2Y1 receptor (P2Y1R), which induces the release of Ca(2+) from intracellular stores via activating phospholipase C through coupling to Gαq. We found that co-expression of anoctamin-1 with the P2Y1R resulted in a small transient increase in Cl(-) conductance in response to ATP. Co-expression of anoctamin-1 with the P2X7R resulted in a large sustained increase in Cl(-) conductance via Ca(2+) influx through the ATP-opened P2X7R in Xenopus and in Axolotl oocytes, which lack endogenous Ca(2+)-dependent Cl(-) channels. P2Y1R- or P2X7R-mediated stimulation of Ano1 was primarily functional, as demonstrated by the absence of a physically stable interaction between Ano1 and the P2X7R. In the pancreatic cell line AsPC-1, we found the same functional Ca(2+)-dependent interaction of P2X7R and Ano1. The P2X7R-mediated sustained activation of Ano1 may be physiologically relevant to the time course of stimulus-secretion coupling in secretory epithelia. No such increase in Cl(-) conductance could be elicited by activating the P2X7 receptor in either Xenopus oocytes or Axolotl oocytes co-expressing Ano6. The lack of function of Ano6 can, at least in part, be explained by its poor cell-surface expression, resulting from a relatively inefficient exit of the homodimeric Ano6 from the endoplasmic reticulum.
Adinolfi,
Trophic activity of a naturally occurring truncated isoform of the P2X7 receptor.
2010, Pubmed
Adinolfi,
Trophic activity of a naturally occurring truncated isoform of the P2X7 receptor.
2010,
Pubmed Adinolfi,
P2X(7) receptor: Death or life?
2005,
Pubmed Allbritton,
Range of messenger action of calcium ion and inositol 1,4,5-trisphosphate.
1992,
Pubmed
,
Xenbase Alonso-Torre,
Calcium responses elicited by nucleotides in macrophages. Interaction between two receptor subtypes.
1993,
Pubmed Amédée,
ATP activates cationic and anionic conductances in Schwann cells cultured from dorsal root ganglia of the mouse.
1995,
Pubmed Arreola,
A novel chloride conductance activated by extracellular ATP in mouse parotid acinar cells.
2003,
Pubmed Becker,
The P2X7 carboxyl tail is a regulatory module of P2X7 receptor channel activity.
2008,
Pubmed
,
Xenbase Boldt,
Glu496Ala polymorphism of human P2X7 receptor does not affect its electrophysiological phenotype.
2003,
Pubmed
,
Xenbase Boton,
Two calcium-activated chloride conductances in Xenopus laevis oocytes permeabilized with the ionophore A23187.
1989,
Pubmed
,
Xenbase Bretschneider,
Nonselective cationic currents elicited by extracellular ATP in human B-lymphocytes.
1995,
Pubmed Browne,
P2X7 receptor channels allow direct permeation of nanometer-sized dyes.
2013,
Pubmed Brunner,
X-ray structure of a calcium-activated TMEM16 lipid scramblase.
2014,
Pubmed Buell,
Blockade of human P2X7 receptor function with a monoclonal antibody.
1998,
Pubmed Caputo,
TMEM16A, a membrane protein associated with calcium-dependent chloride channel activity.
2008,
Pubmed Cervetto,
The P2X7 receptor as a route for non-exocytotic glutamate release: dependence on the carboxyl tail.
2013,
Pubmed Colomar,
ATP stimulation of P2X(7) receptors activates three different ionic conductances on cultured mouse Schwann cells.
2001,
Pubmed Detro-Dassen,
Conserved dimeric subunit stoichiometry of SLC26 multifunctional anion exchangers.
2008,
Pubmed
,
Xenbase Di Virgilio,
P2X(7): a growth-promoting receptor-implications for cancer.
2009,
Pubmed Di Virgilio,
Liaisons dangereuses: P2X(7) and the inflammasome.
2007,
Pubmed Duan,
P2X7 receptor-mediated release of excitatory amino acids from astrocytes.
2003,
Pubmed Duran,
ANOs 3-7 in the anoctamin/Tmem16 Cl- channel family are intracellular proteins.
2012,
Pubmed Egan,
Contribution of calcium ions to P2X channel responses.
2004,
Pubmed Erdahl,
Ca2+ transport properties of ionophores A23187, ionomycin, and 4-BrA23187 in a well defined model system.
1994,
Pubmed Fallah,
TMEM16A(a)/anoctamin-1 shares a homodimeric architecture with CLC chloride channels.
2011,
Pubmed
,
Xenbase Faria,
Pharmacological properties of a pore induced by raising intracellular Ca2+.
2009,
Pubmed Flittiger,
Effects of protons on macroscopic and single-channel currents mediated by the human P2X7 receptor.
2010,
Pubmed
,
Xenbase Galietta,
The TMEM16 protein family: a new class of chloride channels?
2009,
Pubmed Gendreau,
A trimeric quaternary structure is conserved in bacterial and human glutamate transporters.
2004,
Pubmed
,
Xenbase Gloor,
A vector for the synthesis of cRNAs encoding Myc epitope-tagged proteins in Xenopus laevis oocytes.
1995,
Pubmed
,
Xenbase Gomez-Hernandez,
Calcium dependence and distribution of calcium-activated chloride channels in Xenopus oocytes.
1997,
Pubmed
,
Xenbase Griffon,
Molecular determinants of glycine receptor subunit assembly.
1999,
Pubmed
,
Xenbase Grubb,
TMEM16F (Anoctamin 6), an anion channel of delayed Ca(2+) activation.
2013,
Pubmed Grudzien-Nogalska,
Synthesis of anti-reverse cap analogs (ARCAs) and their applications in mRNA translation and stability.
2007,
Pubmed Haeger,
An intramembrane aromatic network determines pentameric assembly of Cys-loop receptors.
2010,
Pubmed Hodges,
Characterization of P2X7 purinergic receptors and their function in rat lacrimal gland.
2009,
Pubmed Huang,
Calcium-activated chloride channel TMEM16A modulates mucin secretion and airway smooth muscle contraction.
2012,
Pubmed Hung,
Roles of protein kinase C in regulation of P2X7 receptor-mediated calcium signalling of cultured type-2 astrocyte cell line, RBA-2.
2005,
Pubmed Kim,
Proteomic and functional evidence for a P2X7 receptor signalling complex.
2001,
Pubmed Klapperstück,
Characteristics of P2X7 receptors from human B lymphocytes expressed in Xenopus oocytes.
2000,
Pubmed
,
Xenbase Klapperstück,
Functional evidence of distinct ATP activation sites at the human P2X(7) receptor.
2001,
Pubmed
,
Xenbase Kmit,
Calcium-activated and apoptotic phospholipid scrambling induced by Ano6 can occur independently of Ano6 ion currents.
2013,
Pubmed Kubick,
The effect of anions on the human P2X7 receptor.
2011,
Pubmed
,
Xenbase Kunzelmann,
Anoctamins.
2011,
Pubmed Kunzelmann,
Molecular functions of anoctamin 6 (TMEM16F): a chloride channel, cation channel, or phospholipid scramblase?
2014,
Pubmed Kuruma,
Dynamics of calcium regulation of chloride currents in Xenopus oocytes.
1999,
Pubmed
,
Xenbase Liu,
Inhibition of Ca(2+)-activated Cl(-) channel ANO1/TMEM16A expression suppresses tumor growth and invasiveness in human prostate carcinoma.
2012,
Pubmed Löhn,
Sodium block and depolarization diminish P2Z-dependent Ca2+ entry in human B lymphocytes.
2001,
Pubmed Machaca,
Reversible Ca gradients between the subplasmalemma and cytosol differentially activate Ca-dependent Cl currents.
1999,
Pubmed
,
Xenbase Mazzone,
Inhibition of cell proliferation by a selective inhibitor of the Ca(2+)-activated Cl(-) channel, Ano1.
2012,
Pubmed Mehta,
ATP-stimulated release of interleukin (IL)-1beta and IL-18 requires priming by lipopolysaccharide and is independent of caspase-1 cleavage.
2001,
Pubmed Nakamoto,
Purinergic P2X7 receptors mediate ATP-induced saliva secretion by the mouse submandibular gland.
2009,
Pubmed Namkung,
Small-molecule activators of TMEM16A, a calcium-activated chloride channel, stimulate epithelial chloride secretion and intestinal contraction.
2011,
Pubmed Nicke,
P2X1 and P2X3 receptors form stable trimers: a novel structural motif of ligand-gated ion channels.
1998,
Pubmed
,
Xenbase Nicke,
Assembly of nicotinic alpha7 subunits in Xenopus oocytes is partially blocked at the tetramer level.
2004,
Pubmed
,
Xenbase Nicke,
A functional P2X7 splice variant with an alternative transmembrane domain 1 escapes gene inactivation in P2X7 knock-out mice.
2009,
Pubmed
,
Xenbase North,
Molecular physiology of P2X receptors.
2002,
Pubmed Novak,
Purinergic signalling in epithelial ion transport: regulation of secretion and absorption.
2011,
Pubmed Paukert,
The P2X(7) receptor from Xenopus laevis: formation of a large pore in Xenopus oocytes.
2002,
Pubmed
,
Xenbase Pelegrin,
Pannexin-1 mediates large pore formation and interleukin-1beta release by the ATP-gated P2X7 receptor.
2006,
Pubmed Pellegatti,
A novel recombinant plasma membrane-targeted luciferase reveals a new pathway for ATP secretion.
2005,
Pubmed Rais,
Two-dimensional electrophoresis for the isolation of integral membrane proteins and mass spectrometric identification.
2004,
Pubmed Ralevic,
Receptors for purines and pyrimidines.
1998,
Pubmed Rassendren,
The permeabilizing ATP receptor, P2X7. Cloning and expression of a human cDNA.
1997,
Pubmed Rath,
Correction factors for membrane protein molecular weight readouts on sodium dodecyl sulfate-polyacrylamide gel electrophoresis.
2013,
Pubmed Reyes,
Na+ modulates anion permeation and block of P2X7 receptors from mouse parotid glands.
2008,
Pubmed Riedel,
Influence of extracellular monovalent cations on pore and gating properties of P2X7 receptor-operated single-channel currents.
2007,
Pubmed
,
Xenbase Riedel,
Kinetics of P2X7 receptor-operated single channels currents.
2007,
Pubmed
,
Xenbase Saiyed,
Molecular basis of gephyrin clustering at inhibitory synapses: role of G- and E-domain interactions.
2007,
Pubmed
,
Xenbase Sauter,
ANO1 (TMEM16A) in pancreatic ductal adenocarcinoma (PDAC).
2015,
Pubmed Schmalzing,
The adhesion molecule on glia (AMOG/beta 2) and alpha 1 subunits assemble to functional sodium pumps in Xenopus oocytes.
1992,
Pubmed
,
Xenbase Schmalzing,
Isoform-specific interactions of Na,K-ATPase subunits are mediated via extracellular domains and carbohydrates.
1997,
Pubmed
,
Xenbase Schreiber,
Expression and function of epithelial anoctamins.
2010,
Pubmed Schroeder,
Expression cloning of TMEM16A as a calcium-activated chloride channel subunit.
2008,
Pubmed
,
Xenbase Schubert,
Multiple ligand-ion solutions: a guide for solution preparation and computer program understanding.
1996,
Pubmed Schwaller,
Cytosolic Ca2+ buffers.
2010,
Pubmed Shimizu,
TMEM16F is a component of a Ca2+-activated Cl- channel but not a volume-sensitive outwardly rectifying Cl- channel.
2013,
Pubmed Solini,
Human primary fibroblasts in vitro express a purinergic P2X7 receptor coupled to ion fluxes, microvesicle formation and IL-6 release.
1999,
Pubmed Stanich,
Ano1 as a regulator of proliferation.
2011,
Pubmed Suadicani,
P2X7 receptors mediate ATP release and amplification of astrocytic intercellular Ca2+ signaling.
2006,
Pubmed Suzuki,
Calcium-dependent phospholipid scrambling by TMEM16F.
2010,
Pubmed Takahashi,
Rat brain serotonin receptors in Xenopus oocytes are coupled by intracellular calcium to endogenous channels.
1987,
Pubmed
,
Xenbase Tian,
Anoctamins are a family of Ca2+-activated Cl- channels.
2012,
Pubmed Tien,
Identification of a dimerization domain in the TMEM16A calcium-activated chloride channel (CaCC).
2013,
Pubmed Tokuyama,
Cloning of rat and mouse P2Y purinoceptors.
1995,
Pubmed
,
Xenbase Valera,
A new class of ligand-gated ion channel defined by P2x receptor for extracellular ATP.
1994,
Pubmed
,
Xenbase von Kügelgen,
Pharmacological profiles of cloned mammalian P2Y-receptor subtypes.
2006,
Pubmed Wang,
Purinergic regulation of CFTR and Ca(2+)-activated Cl(-) channels and K(+) channels in human pancreatic duct epithelium.
2013,
Pubmed Weber,
Endogenous ion channels in oocytes of xenopus laevis: recent developments.
1999,
Pubmed
,
Xenbase Weber,
Ion currents of Xenopus laevis oocytes: state of the art.
1999,
Pubmed
,
Xenbase Wilson,
Epithelial membrane proteins induce membrane blebbing and interact with the P2X7 receptor C terminus.
2002,
Pubmed Yang,
TMEM16A confers receptor-activated calcium-dependent chloride conductance.
2008,
Pubmed
,
Xenbase
