title: Visual neurotransmission in Drosophila requires expression of Fic in glial capitate projections.
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.
authors.affiliation: Department of Neuroscience, University of Texas Southwestern Medical Center, Dallas, TX, USA.
authors.forename: Mokhlasur
authors.initials: M
authors.lastname: Rahman
authors.forename: Hyeilin
authors.initials: H
authors.lastname: Ham
authors.forename: Xinran
authors.initials: X
authors.lastname: Liu
authors.forename: Yoshie
authors.initials: Y
authors.lastname: Sugiura
authors.forename: Kim
authors.initials: K
authors.lastname: Orth
authors.forename: Helmut
authors.initials: H
authors.lastname: Krämer
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D015153:Blotting, Western; D029721:Drosophila Proteins / Q000235:genetics / Q000378:metabolism*; D004331:Drosophila melanogaster / Q000378:metabolism* / Q000648:ultrastructure; D055785:Gene Knockdown Techniques; D006632:Histamine / Q000378:metabolism; D018613:Microscopy, Confocal; D046529:Microscopy, Electron, Transmission; D008969:Molecular Sequence Data; D009154:Mutation; D009457:Neuroglia / Q000378:metabolism* / Q000648:ultrastructure; D018377:Neurotransmitter Agents / Q000378:metabolism; D009713:Nucleotidyltransferases / Q000235:genetics / Q000378:metabolism*; D009899:Optic Lobe, Nonmammalian / Q000378:metabolism / Q000648:ultrastructure; D017956:Photoreceptor Cells, Invertebrate / Q000378:metabolism* / Q000648:ultrastructure; D009435:Synaptic Transmission / Q000502:physiology*; D014796:Visual Perception / Q000502:physiology*
chemical_list: D029721:Drosophila Proteins; D018377:Neurotransmitter Agents; D006632:Histamine; C574946:Fic protein, Drosophila; D009713:Nucleotidyltransferases