The Drosophila G protein‐coupled receptor,Methuselah, exhibits a promiscuous response to peptides |
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| Authors: | William W Ja Gil B Carvalho Marisol Madrigal Richard W Roberts Seymour Benzer |
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| Institution: | 1. Division of Biology, California Institute of Technology, Pasadena, California 91125;2. Department of Chemistry, University of Southern California, Los Angeles, California 90089;3. Mork Family Department of Chemical Engineering, University of Southern California, Los Angeles, California 90089;4. Department of Biological Sciences, University of Southern California, Los Angeles, California 90089;5. Deceased |
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| Abstract: | 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. |
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| Keywords: | alanine‐scanning GPCR methuselah peptide agonists promiscuity |
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