title: The carcinine transporter CarT is required in Drosophila photoreceptor neurons to sustain histamine recycling.
abstract: Synaptic transmission from Drosophila photoreceptors to lamina neurons requires recycling of histamine neurotransmitter. Synaptic histamine is cleared by uptake into glia and conversion into carcinine, which functions as transport metabolite. How carcinine is transported from glia to photoreceptor neurons remains unclear. In a targeted RNAi screen for genes involved in this pathway, we identified carT, which encodes a member of the SLC22A transporter family. CarT expression in photoreceptors is necessary and sufficient for fly vision and behavior. Carcinine accumulates in the lamina of carT flies. Wild-type levels are restored by photoreceptor-specific expression of CarT, and endogenous tagging suggests CarT localizes to synaptic endings. Heterologous expression of CarT in S2 cells is sufficient for carcinine uptake, demonstrating the ability of CarT to utilize carcinine as a transport substrate. Together, our results demonstrate that CarT transports the histamine metabolite carcinine into photoreceptor neurons, thus contributing an essential step to the histamine-carcinine cycle.
authors.affiliation: Department of Neuroscience, University of Texas Southwestern Medical Center, Dallas, United States.
authors.forename: Drew
authors.initials: D
authors.lastname: Stenesen
authors.affiliation: Department of Neuroscience, University of Texas Southwestern Medical Center, Dallas, United States.
authors.forename: Andrew T
authors.initials: AT
authors.lastname: Moehlman
authors.affiliation: Department of Neuroscience, University of Texas Southwestern Medical Center, Dallas, United States.
authors.forename: Helmut
authors.initials: H
authors.lastname: Krämer
mesh_terms: D000818:Animals; D002336:Carnosine / Q000031:analogs & derivatives* / Q000378:metabolism; D004330:Drosophila / Q000502:physiology*; D015870:Gene Expression; D055786:Gene Knockout Techniques; D005820:Genetic Testing; D006632:Histamine / Q000378:metabolism*; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000378:metabolism*; D009457:Neuroglia / Q000378:metabolism; D010786:Photoreceptor Cells / Q000378:metabolism*; D034622:RNA Interference; D000098882:Cocaine- and Amphetamine-Regulated Transcript Protein
chemical_list: D009419:Nerve Tissue Proteins; D000098882:Cocaine- and Amphetamine-Regulated Transcript Protein; D006632:Histamine; D002336:Carnosine; C015055:carcinine
keywords: CRISPR-induced homology-directed repair; D. melanogaster; SLC22 transporter; neuron-glia interactions; neuroscience; neurotransmitter recycling; td-Tomato fusion; vision