title: Lipid flippase modulates olfactory receptor expression and odorant sensitivity in Drosophila.
abstract: In Drosophila melanogaster, the male-specific pheromone cVA (11-cis-vaccenyl acetate) functions as a sex-specific social cue. However, our understanding of the molecular mechanisms underlying cVA pheromone transduction and its regulation are incomplete. Using a genetic screen combined with an electrophysiological assay to monitor pheromone-evoked activity in the cVA-sensing Or67d neurons, we identified an olfactory sensitivity factor encoded by the dATP8B gene, the Drosophila homolog of mammalian ATP8B. dATP8B is expressed in all olfactory neurons that express Orco, the odorant receptor coreceptor, and the odorant responses in most Orco-expressing neurons are reduced. Or67d neurons are severely affected, with strongly impaired cVA-induced responses and lacking spontaneous spiking in the mutants. The dATP8B locus encodes a member of the P4-type ATPase family thought to flip aminophospholipids such as phosphatidylserine and phosphatidylethanolamine from one membrane leaflet to the other. dATP8B protein is concentrated in the cilia of olfactory neuron dendrites, the site of odorant transduction. Focusing on Or67d neuron function, we show that Or67d receptors are mislocalized in dATP8B mutants and that cVA responses can be restored to dATP8B mutants by misexpressing a wild-type dATP8B rescuing transgene, by expressing a vertebrate P4-type ATPase member in the pheromone-sensing neurons or by overexpressing Or67d receptor subunits. These findings reveal an unexpected role for lipid translocation in olfactory receptor expression and sensitivity to volatile odorants.
authors.affiliation: Department of Biomedical Science, Daegu University, Gyeongsan City 712-714, South Korea; and.
authors.forename: Tal Soo
authors.initials: TS
authors.lastname: Ha
authors.affiliation: Departments of Pharmacology and Neuroscience, University of Texas Southwestern Medical Center, Dallas, TX 75390-9111.
authors.forename: Ruohan
authors.initials: R
authors.lastname: Xia
authors.affiliation: Departments of Pharmacology and Neuroscience, University of Texas Southwestern Medical Center, Dallas, TX 75390-9111.
authors.forename: Haiying
authors.initials: H
authors.lastname: Zhang
authors.affiliation: Departments of Pharmacology and Neuroscience, University of Texas Southwestern Medical Center, Dallas, TX 75390-9111 dean.smith@utsouthwestern.edu.
authors.forename: Xin
authors.initials: X
authors.lastname: Jin
authors.affiliation: Departments of Pharmacology and Neuroscience, University of Texas Southwestern Medical Center, Dallas, TX 75390-9111 dean.smith@utsouthwestern.edu.
authors.forename: Dean P
authors.initials: DP
authors.lastname: Smith
mesh_terms: D000818:Animals; D001483:Base Sequence; D017931:DNA Primers / Q000235:genetics; D029721:Drosophila Proteins / Q000235:genetics / Q000378:metabolism*; D004331:Drosophila melanogaster / Q000502:physiology*; D007091:Image Processing, Computer-Assisted; D007150:Immunohistochemistry; D008969:Molecular Sequence Data; D009829:Oleic Acids / Q000378:metabolism*; D010675:Pheromones / Q000378:metabolism*; D049294:Phospholipid Transfer Proteins / Q000235:genetics / Q000378:metabolism*; D011956:Receptors, Cell Surface / Q000378:metabolism*; D018035:Receptors, Odorant / Q000378:metabolism*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D017422:Sequence Analysis, DNA; D012903:Smell / Q000502:physiology*
chemical_list: C518845:11-cis-vaccenyl acetate; C000591168:ATP8B protein, Drosophila; D017931:DNA Primers; D029721:Drosophila Proteins; D009829:Oleic Acids; C530080:Or67d protein, Drosophila; D010675:Pheromones; D049294:Phospholipid Transfer Proteins; D011956:Receptors, Cell Surface; D018035:Receptors, Odorant
keywords: aminophospholipid translocase; olfaction