TY - JOUR
T1 - Visual neurotransmission in Drosophila requires expression of Fic in glial capitate projections
AU - Rahman, Mokhlasur
AU - Ham, Hyeilin
AU - Liu, Xinran
AU - Sugiura, Yoshie
AU - Orth, Kim
AU - Krämer, Helmut
N1 - Funding Information:
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.
PY - 2012/6
Y1 - 2012/6
N2 - 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.
AB - 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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U2 - 10.1038/nn.3102
DO - 10.1038/nn.3102
M3 - Article
C2 - 22544313
AN - SCOPUS:84861578674
SN - 1097-6256
VL - 15
SP - 871
EP - 875
JO - Nature neuroscience
JF - Nature neuroscience
IS - 6
ER -