title: Chloride channels in stellate cells are essential for uniquely high secretion rates in neuropeptide-stimulated Drosophila diuresis.
abstract: Epithelia frequently segregate transport processes to specific cell types, presumably for improved efficiency and control. The molecular players underlying this functional specialization are of particular interest. In Drosophila, the renal (Malpighian) tubule displays the highest per-cell transport rates known and has two main secretory cell types, principal and stellate. Electrogenic cation transport is known to reside in the principal cells, whereas stellate cells control the anion conductance, but by an as-yet-undefined route. Here, we resolve this issue by showing that a plasma membrane chloride channel, encoded by ClC-a, is exclusively expressed in the stellate cell and is required for Drosophila kinin-mediated induction of diuresis and chloride shunt conductance, evidenced by chloride ion movement through the stellate cells, leading to depolarization of the transepithelial potential. By contrast, ClC-a knockdown had no impact on resting secretion levels. Knockdown of a second CLC gene showing highly abundant expression in adult Malpighian tubules, ClC-c, did not impact depolarization of transepithelial potential after kinin stimulation. Therefore, the diuretic action of kinin in Drosophila can be explained by an increase in ClC-a-mediated chloride conductance, over and above a resting fluid transport level that relies on other (ClC-a-independent) mechanisms or routes. This key segregation of cation and anion transport could explain the extraordinary fluid transport rates displayed by some epithelia.
authors.affiliation: Institute of Molecular, Cell and Systems Biology, College of Medical, Veterinary and Life Sciences, University of Glasgow, Glasgow G12 8QQ, United Kingdom;
authors.forename: Pablo
authors.initials: P
authors.lastname: Cabrero
authors.affiliation: Institute of Molecular, Cell and Systems Biology, College of Medical, Veterinary and Life Sciences, University of Glasgow, Glasgow G12 8QQ, United Kingdom;
authors.forename: Selim
authors.initials: S
authors.lastname: Terhzaz
authors.affiliation: Department of Physiology and Biomedical Engineering and.
authors.forename: Michael F
authors.initials: MF
authors.lastname: Romero
authors.affiliation: Institute of Molecular, Cell and Systems Biology, College of Medical, Veterinary and Life Sciences, University of Glasgow, Glasgow G12 8QQ, United Kingdom;
authors.forename: Shireen A
authors.initials: SA
authors.lastname: Davies
authors.affiliation: Department of Biological Sciences, Marquette University, Milwaukee, WI 53201-1881.
authors.forename: Edward M
authors.initials: EM
authors.lastname: Blumenthal
authors.affiliation: Institute of Molecular, Cell and Systems Biology, College of Medical, Veterinary and Life Sciences, University of Glasgow, Glasgow G12 8QQ, United Kingdom; julian.dow@glasgow.ac.uk.
authors.forename: Julian A T
authors.initials: JA
authors.lastname: Dow
mesh_terms: D000818:Animals; D030801:Animals, Genetically Modified; D018118:Chloride Channels / Q000172:deficiency / Q000235:genetics / Q000502:physiology*; D004231:Diuresis / Q000235:genetics / Q000502:physiology*; D029721:Drosophila Proteins / Q000172:deficiency / Q000235:genetics / Q000502:physiology*; D004331:Drosophila melanogaster / Q000166:cytology / Q000235:genetics / Q000502:physiology*; D005260:Female; D055785:Gene Knockdown Techniques; D017344:Genes, Insect; D007705:Kinins / Q000502:physiology; D008297:Male; D008317:Malpighian Tubules / Q000166:cytology / Q000502:physiology; D008954:Models, Biological; D009479:Neuropeptides / Q000502:physiology*
chemical_list: D018118:Chloride Channels; D029721:Drosophila Proteins; D007705:Kinins; D009479:Neuropeptides