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Published November 2009 | public
Journal Article

The Drosophila G protein-coupled receptor, Methuselah, exhibits a promiscuous response to peptides


Methuselah (Mth) is a G protein-coupled receptor (GPCR) associated with longevity in Drosophila melanogaster. Previously, Stunted (Sun) was identified as a peptide agonist of Mth. Here, we identify two additional activators of Mth signaling: Drosophila Sex Peptide (SP) and a novel peptide (Serendipitous Peptide Activator of Mth, SPAM). Minimal functional sequences and key residues were identified from Sun and SPAM by studying truncation and alanine-scanning mutations. These peptide agonists share little sequence homology and illustrate the promiscuity of Mth for activation. mth mutants exhibit no defects in behaviors controlled by SP, casting doubt on the biological significance of Mth activation by any of these agonists, and illustrating the difficulty in applying in vitro studies to their relevance in vivo. Future studies of Mth ligands will help further our understanding of the functional interaction of agonists and GPCRs.

Additional Information

© 2009 The Protein Society. Received: 9 July 2009; Revised: 30 July 2009; Accepted: 31 July 2009. Published online 11 August 2009. The authors thank the Bloomington Drosophila Stock Center for FRT-related fly lines (#7, 7758, and 8136), the Exelixis Collection at Harvard Medical School for P-element insertion lines (e03119 and d05374), the Drosophila Genomics Resource Center for cDNA clones, and X.-Y. Huang (Cornell University Weill Medical College) for the HEK-Mth cell line.

Additional details

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