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.
Ja
William W
WW
Division of Biology, California Institute of Technology, Pasadena, California 91125, USA.
Carvalho
Gil B
GB
Madrigal
Marisol
M
Roberts
Richard W
RW
Benzer
Seymour
S
D000595:Amino Acid Sequence; D000818:Animals; D030801:Animals, Genetically Modified; D029721:Drosophila Proteins / Q000819:agonists / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D007700:Kinetics; D008024:Ligands; D008969:Molecular Sequence Data; D010455:Peptides / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D011485:Protein Binding; D043562:Receptors, G-Protein-Coupled / Q000819:agonists / Q000378:metabolism*; D016415:Sequence Alignment; D015398:Signal Transduction
D029721:Drosophila Proteins; D008024:Ligands; D010455:Peptides; D043562:Receptors, G-Protein-Coupled; C115381:mth protein, Drosophila