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Drosophila odorant receptors are novel seven transmembrane domain proteins that can signal independently of heterotrimeric G proteins

Citation

Smart, R and Kiely, A and Beale, M and Vargas, E and Carraher, C and Kralicek, AV and Christie, DL and Chen, C and Newcomb, RD and Warr, CG, Drosophila odorant receptors are novel seven transmembrane domain proteins that can signal independently of heterotrimeric G proteins, Insect Biochemistry and Molecular Biology, 38, (8) pp. 770-780. ISSN 0965-1748 (2008) [Refereed Article]

DOI: doi:10.1016/j.ibmb.2008.05.002

Abstract

Olfaction in Drosophila is mediated by a large family of membrane-bound odorant receptor proteins (Ors). In heterologous cells, we investigated whether the structural features and signalling mechanisms of ligand-binding Drosophila Ors are consistent with them being G protein-coupled receptors (GPCRs). The detailed membrane topology of Or22a was determined by inserting epitope tags into the termini and predicted loop regions. Immunocytochemistry experiments in Drosophila S2 cells imply that Or22a has seven transmembrane domains but that its membrane topology is opposite to that of GPCRs, with a cytoplasmic N-terminus and extracellular C-terminus. To investigate Or signalling mechanisms, we expressed Or43b in Sf9 and HEK293 cells, and show that inhibitors of heterotrimeric G proteins (GDP-β-S), adenylate cyclase (SQ22536), guanylyl cyclase (ODQ), cyclic nucleotide phosphodiesterases (IBMX) and phospholipase C (U73122) have negligible impact on Or43b responses. Whole cell patching of Or43b/Or83b-transfected HEK293 cells revealed the opening of plasma membrane cation channels on addition of ligand. The response was blocked by lanthanum and by 2-APB, but not by Ruthenium red or SKF96365. Based on these data, we conclude that Drosophila Ors comprise a novel family of seven transmembrane receptors that in HEK293 cells signal by opening cation channels, through a mechanism that is largely independent of G proteins.

Item Details

Item Type:Refereed Article
Keywords:Drosophila; Odorant receptor; Olfaction; Signal transduction; Topology; Transmembrane domain protein; Drosophila protein; guanine nucleotide binding protein; ion channel; OR22a protein, Drosophila; OR43b protein, Drosophila; animal; article; human
Research Division:Biological Sciences
Research Group:Genetics
Research Field:Neurogenetics
Objective Division:Expanding Knowledge
Objective Group:Expanding knowledge
Objective Field:Expanding knowledge in the biological sciences
UTAS Author:Warr, CG (Professor Coral Warr)
ID Code:131970
Year Published:2008
Web of Science® Times Cited:196
Deposited By:Office of the School of Medicine
Deposited On:2019-04-16
Last Modified:2019-04-16
Downloads:0

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