title: A Drosophila orphan G protein-coupled receptor BOSS functions as a glucose-responding receptor: loss of boss causes abnormal energy metabolism.
abstract: Glucose, one of the most important nutrients for animals, acts as a regulatory signal that controls the secretion of hormones, such as insulin, by endocrine tissues. However, how organisms respond to extracellular glucose and how glucose controls nutrient homeostasis remain unknown. Here, we show that a putative Drosophila melanogaster G protein-coupled receptor, previously identified as Bride of sevenless (BOSS), responds to extracellular glucose and regulates sugar and lipid metabolism. We found that BOSS was expressed in the fat body, a nutrient-sensing tissue equivalent to mammalian liver and adipose tissues, and in photoreceptor cells. Boss null mutants had small bodies, exhibited abnormal sugar and lipid metabolism (elevated circulating sugar and lipid levels, impaired lipid mobilization to oenocytes), and were sensitive to nutrient deprivation stress. These phenotypes are reminiscent of flies defective in insulin signaling. Consistent with these findings are the observations that boss mutants had reduced PI3K activity and phospho-AKT levels, which indicates that BOSS is required for proper insulin signaling. Because human G protein-coupled receptor 5B and the seven-transmembrane domain of BOSS share the same sequence, our results also have important implications for glucose metabolism in humans. Thus, our study provides insight not only into the basic mechanisms of metabolic regulation but also into the pathobiological basis for diabetes and obesity.
authors.affiliation: Hirabayashi Research Unit, Chemical Neuroscience Group, Brain Science Institute, RIKEN, Wako-shi, Saitama 351-0198, Japan.
authors.forename: Ayako
authors.initials: A
authors.lastname: Kohyama-Koganeya
authors.forename: Yeon-Jeong
authors.initials: YJ
authors.lastname: Kim
authors.forename: Masayuki
authors.initials: M
authors.lastname: Miura
authors.forename: Yoshio
authors.initials: Y
authors.lastname: Hirabayashi
mesh_terms: D000273:Adipose Tissue / Q000378:metabolism; D000818:Animals; D004330:Drosophila / Q000378:metabolism*; D029721:Drosophila Proteins / Q000235:genetics / Q000502:physiology*; D004734:Energy Metabolism; D005136:Eye Proteins / Q000235:genetics / Q000502:physiology*; D005947:Glucose / Q000378:metabolism*; D006801:Humans; D007328:Insulin / Q000378:metabolism; D050356:Lipid Metabolism; D008066:Lipolysis; D008562:Membrane Glycoproteins / Q000235:genetics / Q000502:physiology*; D051379:Mice; D009154:Mutation; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D018000:Receptors, Peptide / Q000235:genetics / Q000502:physiology*; D015398:Signal Transduction
chemical_list: D029721:Drosophila Proteins; D005136:Eye Proteins; D007328:Insulin; D008562:Membrane Glycoproteins; D018000:Receptors, Peptide; C072141:boss protein, Drosophila; D019869:Phosphatidylinositol 3-Kinases; D005947:Glucose