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      secCl is a cys-loop ion channel necessary for the chloride conductance that mediates hormone-induced fluid secretion in Drosophila

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          Abstract

          Organisms use circulating diuretic hormones to control water balance (osmolarity), thereby avoiding dehydration and managing excretion of waste products. The hormones act through G-protein-coupled receptors to activate second messenger systems that in turn control the permeability of secretory epithelia to ions like chloride. In insects, the chloride channel mediating the effects of diuretic hormones was unknown. Surprisingly, we find a pentameric, cys-loop chloride channel, a type of channel normally associated with neurotransmission, mediating hormone-induced transepithelial chloride conductance. This discovery is important because: 1) it describes an unexpected role for pentameric receptors in the membrane permeability of secretory epithelial cells, and 2) it suggests that neurotransmitter-gated ion channels may have evolved from channels involved in secretion.

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          Most cited references39

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          Using FlyAtlas to identify better Drosophila melanogaster models of human disease.

          FlyAtlas, a new online resource, provides the most comprehensive view yet of expression in multiple tissues of Drosophila melanogaster. Meta-analysis of the data shows that a significant fraction of the genome is expressed with great tissue specificity in the adult, demonstrating the need for the functional genomic community to embrace a wide range of functional phenotypes. Well-known developmental genes are often reused in surprising tissues in the adult, suggesting new functions. The homologs of many human genetic disease loci show selective expression in the Drosophila tissues analogous to the affected human tissues, providing a useful filter for potential candidate genes. Additionally, the contributions of each tissue to the whole-fly array signal can be calculated, demonstrating the limitations of whole-organism approaches to functional genomics and allowing modeling of a simple tissue fractionation procedure that should improve detection of weak or tissue-specific signals.
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            Genetic transformation of Drosophila with transposable element vectors

            Exogenous DNA sequences were introduced into the Drosophila germ line. A rosy transposon (ry1), constructed by inserting a chromosomal DNA fragment containing the wild-type rosy gene into a P transposable element, transformed germ line cells in 20 to 50 percent of the injected rosy mutant embryos. Transformants contained one or two copies of chromosomally integrated, intact ry1 that were stably inherited in subsequent generations. These transformed flies had wild-type eye color indicating that the visible genetic defect in the host strain could be fully and permanently corrected by the transferred gene. To demonstrate the generality of this approach, a DNA segment that does not confer a recognizable phenotype on recipients was also transferred into germ line chromosomes.
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              Recent advances in Cys-loop receptor structure and function.

              Throughout the nervous system, moment-to-moment communication relies on postsynaptic receptors to detect neurotransmitters and change the membrane potential. For the Cys-loop superfamily of receptors, recent structural data have catalysed a leap in our understanding of the three steps of chemical-to-electrical transduction: neurotransmitter binding, communication between the binding site and the barrier to ions, and opening and closing of the barrier. The emerging insights might be expected to explain how mutations of receptors cause neurological disease, but the opposite is generally true. Namely, analyses of disease-causing mutations have clarified receptor structure-function relationships as well as mechanisms governing the postsynaptic response.
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                Author and article information

                Contributors
                joseph.dent@mcgill.ca
                Journal
                Sci Rep
                Sci Rep
                Scientific Reports
                Nature Publishing Group UK (London )
                2045-2322
                16 May 2019
                16 May 2019
                2019
                : 9
                : 7464
                Affiliations
                [1 ]ISNI 0000 0004 1936 8649, GRID grid.14709.3b, Department of Biology, , McGill University, 1205 Dr. Penfield, Montréal, ; Québec, H3A 1B1 Canada
                [2 ]ISNI 0000000123222966, GRID grid.6936.a, Institute of Neuroscience, Technische Universität München, Biedersteiner Str. 29, ; München, Bau 601D-80802 Germany
                [3 ]ISNI 0000 0004 1936 8227, GRID grid.25073.33, Department of Biology, , McMaster University, 1280 Main Street West, Hamilton, ; Ontario, L8S 4K1 Canada
                [4 ]ISNI 0000 0001 2292 3357, GRID grid.14848.31, Department of Neurosciences, , Research Centre of the University of Montréal Hospital Centre, Montréal, ; Québec, Canada
                [5 ]Max Planck Institute of Neurobiology, Sensorimotor Control Research Group, Am Klopferspitz 18, Martinsried, 82152 Germany
                Author information
                http://orcid.org/0000-0001-5817-5426
                Article
                42849
                10.1038/s41598-019-42849-9
                6522505
                31097722
                1411a4b6-2d06-44ab-9e28-5d3aa7ef5558
                © The Author(s) 2019

                Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.

                History
                : 25 June 2018
                : 10 April 2019
                Funding
                Funded by: Natural Science and Engineering Research Council 401634-10 Chemtura Canada Co.
                Categories
                Article
                Custom metadata
                © The Author(s) 2019

                Uncategorized
                molecular evolution,neurophysiology
                Uncategorized
                molecular evolution, neurophysiology

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