Sugar Sensor

Science Signaling  14 Oct 2008:
Vol. 1, Issue 41, pp. ec353
DOI: 10.1126/scisignal.141ec353

BOSS (bride of sevenless) is not your average signaling protein. It belongs to the family of heterotrimeric guanine nucleotide-binding proteins characterized by their seven transmembrane-spanning segments. But BOSS was originally characterized for its role in differentiation of the eye in Drosophila, not as a receptor but rather as a ligand for the receptor tyrosine kinase Sevenless. Whether it has its own ligand or what its own receptor function might be was unclear until Kohyama-Koganeya et al. tracked down the reason for the reduced size of boss-deficient flies. They detected abundant expression of BOSS in the fat body, the fly equivalent of the liver in mammals. Another hint as to BOSS’s function was that a BLAST search showed similarity to the trehalose taste receptor and a transporter molecule (CG152210) that carries small molecules, including sugars. When transfected into human HEK293 cells, BOSS conferred activation of a reporter gene in response to glucose but not to other sugars. BOSS was also internalized after exposure of cells to glucose. Mutant boss1 flies had reduced amounts of circulating sugar and lipid in the hemolymph and increased amounts of triacylglycerol, indicative of impaired lipid metabolism. These characteristics are shared by flies with disrupted insulin signaling, and indeed boss mutant flies showed reduced activity of phosphoinositide 3-kinase and reduced phosphorylation of the kinase Akt, enzymes normally activated in response to insulin. The authors point out that humans have a receptor, GPRC5B, that shares sequence similarity with BOSS. Thus, they propose that the role of BOSS as a glucose sensor could be relevant to understanding disorders like obesity and diabetes.

A. Kohyama-Koganeya, Y.-J. Kim, M. Miura, Y. Hirabayashi, A Drosophila orphan G-protein coupled receptor BOSS functions as a glucose-responding receptor: Loss of boss causes abnormal energy metabolism. Proc. Natl. Acad. Sci. U.S.A. 105, 15328-15333 (2008). [Abstract] [Full Text]