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Visual neurotransmission in Drosophila requires expression of Fic in glial capitate projections

Nature Neuroscience volume 15, pages 871875 (2012) | Download Citation

Abstract

Fic domains can catalyze the addition of adenosine monophosphate to target proteins. To date, the function of Fic domain proteins in eukaryotic physiology remains unknown. We generated genetic models of the single Drosophila Fic domain–containing protein, Fic. Flies lacking Fic were viable and fertile, but blind. Photoreceptor cells depolarized normally following light stimulation, but failed to activate postsynaptic neurons, as indicated by the loss of ON transients in electroretinograms, consistent with a neurotransmission defect. Functional rescue of neurotransmission required expression of enzymatically active Fic on capitate projections of glia cells, but not neurons, supporting a role in the recycling of the visual neurotransmitter histamine. Histamine levels were reduced in the lamina of Fic null flies, and dietary histamine partially restored ON transients. These findings establish a previously unknown regulatory mechanism in visual neurotransmission and provide, to the best of our knowledge, the first evidence for a role of glial capitate projections in neurotransmitter recycling.

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Acknowledgements

We are grateful to R. Hiesinger for help and advice with the ERG measurements and the use of his ERG setup, W. Pak, B. Hoveman and the Bloomington Stock center for fly lines, M. Buszczak for antibodies, C. Gilpin from the Molecular and Cellular Imaging Facility at UT Southwestern, S.H. Kim and B. Tu for technical help, and to E. Kavalali and A. Haberman for helpful discussions. This work was supported by grants to H.K. from the US National Institutes of Health National Eye Institute (EY10199 and EY021922) and Visual Science Core grant EY020799. K.O. and H.H. are supported by grants from the US National Institutes of Health (Allergy and Infectious Disease, R01-AI056404 and R01-AI087808) and the Welch Foundation (I-1561). K.O. is a Burroughs Wellcome Investigator in Pathogenesis of Infectious Disease and a W.W. Caruth Jr. Biomedical Scholar.

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Affiliations

  1. Department of Neuroscience, University of Texas Southwestern Medical Center, Dallas, Texas, USA.

    • Mokhlasur Rahman
    • , Xinran Liu
    • , Yoshie Sugiura
    •  & Helmut Krämer
  2. Department of Molecular Biology, University of Texas Southwestern Medical Center, Dallas, Texas, USA.

    • Hyeilin Ham
    •  & Kim Orth
  3. Department of Cell Biology, University of Texas Southwestern Medical Center, Dallas, Texas, USA.

    • Helmut Krämer

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Contributions

M.R. and H.K. performed the fly genetic studies. X.L. and Y.S. performed the electron microscopy studies. H.H. performed the molecular biology and biochemistry studies. H.K., M.R. and K.O. designed the study and analyzed the data. H.K. and K.O. wrote the paper. All of the authors discussed the results and commented on the manuscript.

Competing interests

The authors declare no competing financial interests.

Corresponding author

Correspondence to Helmut Krämer.

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DOI

https://doi.org/10.1038/nn.3102

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