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PNAS 105 (40): 15328-15333

Copyright © 2008 by the National Academy of Sciences.


BIOLOGICAL SCIENCES / BIOCHEMISTRY

A Drosophila orphan G protein-coupled receptor BOSS functions as a glucose-responding receptor: Loss of boss causes abnormal energy metabolism

Ayako Kohyama-Koganeya*,{dagger}, Yeon-Jeong Kim*, Masayuki Miura{dagger},{ddagger}, and Yoshio Hirabayashi*,{ddagger},§

*Hirabayashi Research Unit, Chemical Neuroscience Group, Brain Science Institute, RIKEN, Wako-shi, Saitama 351-0198, Japan; {dagger}Department of Genetics, Graduate School of Pharmaceutical Sciences, University of Tokyo, Tokyo 113-0033, Japan; and {ddagger}Core Research for Evolutional Science and Technology, Japan Science and Technology Agency, Tokyo 113-0033, Japan

Communicated by Sen-itiroh Hakomori, Pacific Northwest Research Institute and University of Washington, Seattle, WA, August 15, 2008

Received for publication April 18, 2008.

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.

Key Words: energy homeostasis • fat body • insulin signaling


Author contributions: A.K.-K., M.M., and Y.H. designed research; A.K.-K., Y.-J.K., and Y.H. performed research; A.K.-K. and Y.H. analyzed data; and A.K.-K. and Y.H. wrote the paper.

The authors declare no conflict of interest.

This article contains supporting information online at www.pnas.org/cgi/content/full/0807833105/DCSupplemental.

§To whom correspondence should be addressed. E-mail: hirabaya{at}riken.jp

© 2008 by The National Academy of Sciences of the USA


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