Identification of a novel insect neuropeptide, CNMa and its receptor

• Published in: FEBS letters Vol. 588; no. 12; pp. 2037 - 2041
• Main Authors: Jung, Sung-Hwan, Lee, Jae-Hyuk, Chae, Hyo-Seok, Seong, Jae Young, Park, Yoonseong, Park, Zee-Yong, Kim, Young-Joon
• Format: Journal Article
• Language: English
• Published: England Elsevier B.V 05.06.2014
• Subjects: Amino Acid Sequence; Animals; Apis mellifera; Arthropoda; Bombyx; CHO Cells; Cricetinae; Cricetulus; Drosophila; Drosophila melanogaster; Drosophila melanogaster - genetics; Drosophila Proteins - chemistry; Drosophila Proteins - metabolism; Evolution, Molecular; G protein-coupled receptor; Lepidoptera; Ligands; Molecular Sequence Data; Neurons - metabolism; Neuropeptide; Neuropeptides - chemistry; Neuropeptides - metabolism; Orphan GPCR; Phylogeny; Receptors, Neuropeptide - chemistry; Receptors, Neuropeptide - metabolism; G protein-coupled receptor; Orphan GPCR; Neuropeptide; Drosophila; Bombyx
• ISSN: 0014-5793; 1873-3468
• DOI: 10.1016/j.febslet.2014.04.028

•CNMa is a small cyclic neuropeptide, highly conserved in most arthropod species.•CNMa is a highly potent and selective ligand for the orphan GPCR, CG33696 (CNMaR).•CNMa is expressed in the central nervous system.•Two clades of CNMaR occur in arthropod genomes, but many taxa retain only one.•Lepidoptera retains CNMaR, but no CNMa. A moth CNMaR is not sensitive to CNMa. To identify ligands for orphan GPCRs, we searched novel neuropeptide genes in the Drosophila melanogaster genome. Here, we describe CNMa, a novel cyclic neuropeptide that is a highly potent and selective agonist for the orphan GPCR, CG33696 (CNMaR). Phylogenetic analysis revealed that arthropod species have two paralogous CNMaRs, but many taxa retain only one. Drosophila CNMa potently activates CNMaR-2 from Apis mellifera, suggesting both receptors are functional. Although CNMa is conserved in most arthropods, Lepidoptera lack the CNMa gene. However, they retain the CNMaR gene. Bombyx CNMaR showed low sensitivity to Drosophila CNMa, hinting toward the existence of additional CNMaR ligand(s).