@article{aee70e60c5b34353bb1620b50988e548,
title = "The glial sodium-potassium-2-chloride cotransporter is required for synaptic transmission in the Drosophila visual system",
abstract = " The Drosophila Ncc69 gene encodes a Na + -K + -2Cl − -cotransporter (NKCC) that is critical for regulating intra- and extracellular ionic conditions in different tissues. Here, we show that the Ncc69 transporter is necessary for fly vision and that its expression is required non-autonomously in glia to maintain visual synaptic transmission. Flies mutant for Ncc69 exhibit normal photoreceptor depolarization in response to a light pulse but lack the ON and OFF-transients characteristic of postsynaptic responses of lamina neurons, indicating a failure in synaptic transmission. We also find that synaptic transmission requires the Ncc69 regulatory kinases WNK and Fray in glia. The ERG phenotype is associated with a defect in the recycling of the histamine neurotransmitter. Ncc69 mutants exhibit higher levels of the transport metabolite carcinine in lamina cartridges, with its accumulation most intense in the extracellular space. Our work reveals a novel role of glial NKCC transporters in synaptic transmission, possibly through regulating extracellular ionic conditions.",
author = "Drew Stenesen and Moehlman, {Andrew T.} and Schellinger, {Jeffrey N.} and Rodan, {Aylin R.} and Helmut Kr{\"a}mer",
note = "Funding Information: We would like to thank the Kr{\"a}mer lab for helpful comments and the Bloomington Stock Center (supported by NIH P40OD018537), the Berkeley Drosophila Genome Project, the Drosophila Genomics Resource Center (supported by NIH grant 2P40OD010949), and the Vienna Drosophila Resource Center for fly stocks and reagents, Billy Leiserson (Yale University) for Ncc69 mutant and UAS-Ncc69 flies, Jim Turner (NIH) for the anti-Ncc69 antibody, Johannes Bischof and Konrad Basler (University of Zurich) for the pUASg.attB plasmid, and Chou-Long Huang (UT Southwestern) for the mammalian WNK cDNAs. We thank the Molecular and Cellular Imaging Facility at the University of Texas Southwestern Medical center for help with electron microscopy (NIH S10 OD020103). FlyBase provided important information used in this work. This work was supported by grants from the National Institutes of Health (EY010199 and GM120196) to H. K., and (DK091316 and DK110358) to A.R.R., core grant EY020799, NIDA T32-DA07290, Basic Science Training Program in Drug Abuse Research supporting D.S., and NIGMS T32-GM008203, Cell and Molecular Biology Training Grant supporting A.T.M., and from the American Heart Association (16CSA2853002 to A.R.R.). Publisher Copyright: {\textcopyright} 2019, The Author(s).",
year = "2019",
month = dec,
day = "1",
doi = "10.1038/s41598-019-38850-x",
language = "English (US)",
volume = "9",
journal = "Scientific Reports",
issn = "2045-2322",
publisher = "Nature Publishing Group",
number = "1",
}