title: The orphan pentameric ligand-gated ion channel pHCl-2 is gated by pH and regulates fluid secretion in Drosophila Malpighian tubules.
abstract: Pentameric ligand-gated ion channels (pLGICs) constitute a large protein superfamily in metazoa whose role as neurotransmitter receptors mediating rapid, ionotropic synaptic transmission has been extensively studied. Although the vast majority of pLGICs appear to be neurotransmitter receptors, the identification of pLGICs in non-neuronal tissues and homologous pLGIC-like proteins in prokaryotes points to biological functions, possibly ancestral, that are independent of neuronal signalling. Here, we report the molecular and physiological characterization of a highly divergent, orphan pLGIC subunit encoded by the pHCl-2 (CG11340) gene, in Drosophila melanogaster We show that pHCl-2 forms a channel that is insensitive to a wide array of neurotransmitters, but is instead gated by changes in extracellular pH. pHCl-2 is expressed in the Malpighian tubules, which are non-innervated renal-type secretory tissues. We demonstrate that pHCl-2 is localized to the apical membrane of the epithelial principal cells of the tubules and that loss of pHCl-2 reduces urine production during diuresis. Our data implicate pHCl-2 as an important source of chloride conductance required for proper urine production, highlighting a novel role for pLGICs in epithelial tissues regulating fluid secretion and osmotic homeostasis.
authors.affiliation: Department of Biology, McGill University, 1205 Dr Penfield, Montreal, QC, Canada H3A 1B1.
authors.forename: Daniel
authors.initials: D
authors.lastname: Feingold
authors.affiliation: Institute of Neuroscience, Technische Universität München, Biedersteiner Strasse 29, München Bau 601D-80802, Germany.
authors.forename: Tanja
authors.initials: T
authors.lastname: Starc
authors.affiliation: Department of Biology, McMaster University, 1280 Main Street West, Hamilton, ON, Canada L8S 4K1.
authors.forename: Michael J
authors.initials: MJ
authors.lastname: O'Donnell
authors.affiliation: Department of Biology, McGill University, 1205 Dr Penfield, Montreal, QC, Canada H3A 1B1.
authors.forename: Laura
authors.initials: L
authors.lastname: Nilson
authors.affiliation: Department of Biology, McGill University, 1205 Dr Penfield, Montreal, QC, Canada H3A 1B1 joseph.dent@mcgill.ca.
authors.forename: Joseph A
authors.identifier: 0000-0001-5817-5426
authors.initials: JA
authors.lastname: Dent
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D001826:Body Fluids / Q000378:metabolism*; D018118:Chloride Channels / Q000378:metabolism; D000242:Cyclic AMP / Q000494:pharmacology; D004231:Diuresis / Q000187:drug effects; D029721:Drosophila Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D004331:Drosophila melanogaster / Q000187:drug effects / Q000378:metabolism*; D004847:Epithelial Cells / Q000187:drug effects / Q000378:metabolism; D006863:Hydrogen-Ion Concentration / Q000187:drug effects; D058446:Ligand-Gated Ion Channels / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D008317:Malpighian Tubules / Q000187:drug effects / Q000378:metabolism*; D008954:Models, Biological; D009154:Mutation / Q000235:genetics; D021122:Protein Subunits / Q000737:chemistry / Q000378:metabolism
chemical_list: D018118:Chloride Channels; D029721:Drosophila Proteins; D058446:Ligand-Gated Ion Channels; D021122:Protein Subunits; D000242:Cyclic AMP
keywords: Cys-loop ligand-gated ion channel; Diuresis; Renal; pLGIC