Click here to close
Hello! We notice that you are using Internet Explorer, which is not supported by Xenbase and may cause the site to display incorrectly.
We suggest using a current version of Chrome,
FireFox, or Safari.
J Biol Chem
2014 May 23;28921:15130-40. doi: 10.1074/jbc.M113.525576.
Show Gene links
Show Anatomy links
An internally modulated, thermostable, pH-sensitive Cys loop receptor from the hydrothermal vent worm Alvinella pompejana.
Juneja P
,
Horlacher R
,
Bertrand D
,
Krause R
,
Marger F
,
Welte W
.
???displayArticle.abstract???
Cys loop receptors (CLRs) are commonly known as ligand-gated channels that transiently open upon binding of neurotransmitters to modify the membrane potential. However, a class of cation-selective bacterial homologues of CLRs have been found to open upon a sudden pH drop, suggesting further ligands and more functions of the homologues in prokaryotes. Here we report an anion-selective CLR from the hydrothermal vent annelid worm Alvinella pompejana that opens at low pH. A. pompejana expressed sequence tag databases were explored by us, and two full-length CLR sequences were identified, synthesized, cloned, expressed in Xenopus oocytes, and studied by two-electrode voltage clamp. One channel, named Alv-a1-pHCl, yielded functional receptors and opened upon a sudden pH drop but not by other known agonists. Sequence comparison showed that both CLR proteins share conserved characteristics with eukaryotic CLRs, such as an N-terminal helix, a cysteine loop motif, and an intracellular loop intermediate in length between the long loops of other eukaryotic CLRs and those of prokaryotic CLRs. Both full-length Alv-a1-pHCl and a truncated form, termed tAlv-a1-pHCl, lacking 37 amino-terminal residues that precede the N-terminal helix, formed functional channels in oocytes. After pH activation, tAlv-a1-pHCl showed desensitization and was not modulated by ivermectin. In contrast, pH-activated, full-length Alv-a1-pHCl showed a marked rebound current and was modulated significantly by ivermectin. A thermostability assay indicated that purified tAlv-a1-pHCl expressed in Sf9 cells denatured at a higher temperature than the nicotinic acetylcholine receptor from Torpedo californica.
Anisimova,
Approximate likelihood-ratio test for branches: A fast, accurate, and powerful alternative.
2006, Pubmed
Anisimova,
Approximate likelihood-ratio test for branches: A fast, accurate, and powerful alternative.
2006,
Pubmed
Bar-Lev,
Molecular dissection of Cl--selective Cys-loop receptor points to components that are dispensable or essential for channel activity.
2011,
Pubmed
Beg,
Protons act as a transmitter for muscle contraction in C. elegans.
2008,
Pubmed
Bocquet,
A prokaryotic proton-gated ion channel from the nicotinic acetylcholine receptor family.
2007,
Pubmed
,
Xenbase
Bocquet,
X-ray structure of a pentameric ligand-gated ion channel in an apparently open conformation.
2009,
Pubmed
Brownlee,
Actions of the anthelmintic ivermectin on the pharyngeal muscle of the parasitic nematode, Ascaris suum.
1997,
Pubmed
Celie,
Nicotine and carbamylcholine binding to nicotinic acetylcholine receptors as studied in AChBP crystal structures.
2004,
Pubmed
Corringer,
Structure and pharmacology of pentameric receptor channels: from bacteria to brain.
2012,
Pubmed
Dereeper,
Phylogeny.fr: robust phylogenetic analysis for the non-specialist.
2008,
Pubmed
Duret,
Functional prokaryotic-eukaryotic chimera from the pentameric ligand-gated ion channel family.
2011,
Pubmed
,
Xenbase
Edgar,
MUSCLE: multiple sequence alignment with high accuracy and high throughput.
2004,
Pubmed
Gagnière,
Insights into metazoan evolution from Alvinella pompejana cDNAs.
2010,
Pubmed
Gaill,
Structural comparison of cuticle and interstitial collagens from annelids living in shallow sea-water and at deep-sea hydrothermal vents.
1995,
Pubmed
Gondhalekar,
Mechanisms underlying fipronil resistance in a multiresistant field strain of the German cockroach (Blattodea: Blattellidae).
2012,
Pubmed
Guindon,
New algorithms and methods to estimate maximum-likelihood phylogenies: assessing the performance of PhyML 3.0.
2010,
Pubmed
Heuberger,
Oligomeric state of membrane transport proteins analyzed with blue native electrophoresis and analytical ultracentrifugation.
2002,
Pubmed
Hibbs,
Principles of activation and permeation in an anion-selective Cys-loop receptor.
2011,
Pubmed
Hoda,
Human nocturnal frontal lobe epilepsy: pharmocogenomic profiles of pathogenic nicotinic acetylcholine receptor beta-subunit mutations outside the ion channel pore.
2008,
Pubmed
,
Xenbase
Hogg,
An automated system for intracellular and intranuclear injection.
2008,
Pubmed
,
Xenbase
Holder,
Deep transcriptome-sequencing and proteome analysis of the hydrothermal vent annelid Alvinella pompejana identifies the CvP-bias as a robust measure of eukaryotic thermostability.
2013,
Pubmed
Hu,
An interaction involving an arginine residue in the cytoplasmic domain of the 5-HT3A receptor contributes to receptor desensitization mechanism.
2006,
Pubmed
,
Xenbase
Hurst,
A novel positive allosteric modulator of the alpha7 neuronal nicotinic acetylcholine receptor: in vitro and in vivo characterization.
2005,
Pubmed
,
Xenbase
Jensen,
Charge selectivity of the Cys-loop family of ligand-gated ion channels.
2005,
Pubmed
Karlin,
Emerging structure of the nicotinic acetylcholine receptors.
2002,
Pubmed
Kashiwagi,
Characterization of a Y-Family DNA Polymerase eta from the Eukaryotic Thermophile Alvinella pompejana.
2010,
Pubmed
Kelley,
A cytoplasmic region determines single-channel conductance in 5-HT3 receptors.
2003,
Pubmed
Krause,
Ivermectin: a positive allosteric effector of the alpha7 neuronal nicotinic acetylcholine receptor.
1998,
Pubmed
,
Xenbase
McCavera,
An ivermectin-sensitive glutamate-gated chloride channel from the parasitic nematode Haemonchus contortus.
2009,
Pubmed
,
Xenbase
McKinnon,
Length and amino acid sequence of peptides substituted for the 5-HT3A receptor M3M4 loop may affect channel expression and desensitization.
2012,
Pubmed
,
Xenbase
Millar,
RIC-3: a nicotinic acetylcholine receptor chaperone.
2008,
Pubmed
Miyazawa,
Structure and gating mechanism of the acetylcholine receptor pore.
2003,
Pubmed
Mounsey,
Molecular characterisation of a pH-gated chloride channel from Sarcoptes scabiei.
2007,
Pubmed
,
Xenbase
O'Toole,
Discrete M3-M4 intracellular loop subdomains control specific aspects of γ-aminobutyric acid type A receptor function.
2011,
Pubmed
Papke,
Activation and desensitization of nicotinic alpha7-type acetylcholine receptors by benzylidene anabaseines and nicotine.
2009,
Pubmed
,
Xenbase
Schnizler,
A novel chloride channel in Drosophila melanogaster is inhibited by protons.
2005,
Pubmed
,
Xenbase
Shan,
Ivermectin, an unconventional agonist of the glycine receptor chloride channel.
2001,
Pubmed
Silberberg,
Ivermectin Interaction with transmembrane helices reveals widespread rearrangements during opening of P2X receptor channels.
2007,
Pubmed
,
Xenbase
Sine,
Recent advances in Cys-loop receptor structure and function.
2006,
Pubmed
Smart,
Synaptic neurotransmitter-gated receptors.
2012,
Pubmed
Tasneem,
Identification of the prokaryotic ligand-gated ion channels and their implications for the mechanisms and origins of animal Cys-loop ion channels.
2005,
Pubmed
Thompson,
The pharmacological profile of ELIC, a prokaryotic GABA-gated receptor.
2012,
Pubmed
,
Xenbase
Velisetty,
Desensitization mechanism in prokaryotic ligand-gated ion channel.
2012,
Pubmed
Wolstenholme,
Glutamate-gated chloride channels and the mode of action of the avermectin/milbemycin anthelmintics.
2005,
Pubmed
Wooltorton,
Pharmacological and physiological characterization of murine homomeric beta3 GABA(A) receptors.
1997,
Pubmed
,
Xenbase