| Title: | Lipid flippase modulates olfactory receptor expression and odorant sensitivity in Drosophila |
| Author(s): | Ha TS; Xia R; Zhang H; Jin X; Smith DP; |
| Address: | "Department of Biomedical Science, Daegu University, Gyeongsan City 712-714, South Korea; and. Departments of Pharmacology and Neuroscience, University of Texas Southwestern Medical Center, Dallas, TX 75390-9111. Departments of Pharmacology and Neuroscience, University of Texas Southwestern Medical Center, Dallas, TX 75390-9111 dean.smith@utsouthwestern.edu" |
| ISSN/ISBN: | 1091-6490 (Electronic) 0027-8424 (Print) 0027-8424 (Linking) |
| 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" |
| Keywords: | "Animals Base Sequence DNA Primers/genetics Drosophila Proteins/genetics/*metabolism Drosophila melanogaster/*physiology Image Processing, Computer-Assisted Immunohistochemistry Molecular Sequence Data Oleic Acids/*metabolism Pheromones/*metabolism Phospho;neuroscience;" |
| Notes: | "MedlineHa, Tal Soo Xia, Ruohan Zhang, Haiying Jin, Xin Smith, Dean P eng DCD011751/PHS HHS/ R01 DC011751/DC/NIDCD NIH HHS/ DC002539/DC/NIDCD NIH HHS/ R01 DC015230/DC/NIDCD NIH HHS/ R01 DC002539/DC/NIDCD NIH HHS/ Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't 2014/05/14 Proc Natl Acad Sci U S A. 2014 May 27; 111(21):7831-6. doi: 10.1073/pnas.1401938111. Epub 2014 May 12" |
