Bombyx neuropeptide G protein-coupled receptor A14 and A15 are two functional G protein-coupled receptors for CCHamide neuropeptides. (April 2021)

• Record Type: Journal Article
• Authors: Tian, Yanan; Jiang, Chaohui; Pan, Yi; Guo, Zhiqiang; Wang, Weiwei; Luo, Xumei; Cao, Zheng; Zhang, Bing; Yang, Jingwen; Shi, Ying; Zhou, Naiming; He, Xiaobai
• Is Part Of: Insect biochemistry and molecular biology. Volume 131(2021)
• Publication Date: 2021-04
• Subjects: CCHamide -- Bombyx mori -- G protein-coupled receptor (GPCR) -- Neuropeptide -- Cell signaling -- ERK1/2; Insect biochemistry -- Periodicals; Insects -- Physiology -- Periodicals; Insects -- Molecular aspects -- Periodicals; Biochemistry -- Periodicals; Insectes -- Biochimie -- Périodiques; Insectes -- Composition -- Périodiques; Insectes -- Physiologie -- Périodiques; Insectes -- Aspect moléculaire -- Périodiques; Biochimie -- Périodiques; Biochemistry; Insect biochemistry; Insects -- Molecular aspects; Insects -- Physiology; Periodicals; 572.8157
• DOI: 10.1016/j.ibmb.2021.103553
• Languages: English
• ISSNs: 0965-1748

Abstract

Abstract: CCHamides are newly identified insect neuropeptides, which are widely occurring in most insects. However, our knowledge about their signaling characteristics and physiological roles is still limited. Here, we cloned two full-length cDNAs encoding putative CCHamide receptors, Bombyx neuropeptide GPCR A14 (BNGR-A14) and -A15 (BNGR-A15), from the brain of B. mori larvae. Characterization of signaling indicated that Bombyx CCHamide-1 and CCHamide-2 are specific endogenous ligands for BNGR-A15 and BNGR-A14, respectively. Further functional assays combined with specific inhibitors demonstrated that upon activation by CCHamide-2, BNGR-A14 elicited significant increases in CRE-driven luciferase activity, intracellular Ca 2+ mobilization and ERK1/2 phosphorylation in a Gq inhibitor-sensitive manner, while BNGR-A15 was activated by CCHamide-1, thus leading to intracellular accumulation of cAMP, Ca 2+ mobilization, and ERK1/2 phosphorylation in a Gs and Gq inhibitor-sensitive manner. Based on these findings, we designated the receptors BNGR-A15 and -A14 as Bommo -CCHaR-1 and -2, respectively. In addition, our results showed that CCHamides are considered to require intrachain disulfide bonds to activate their respective receptor in the physiological concentration range. Moreover, quantitative RT-PCR analysis revealed that CCHamide-1 is more likely to serve as a brain-gut peptide to regulate feeding behavior and growth through BNGR-A15, whereas the CCHamide-2 signaling system might play an important role in the control of multiple physiological processes. Our findings provide in-depth information on CCHamide-1 and -2-mediated signaling, facilitating further elucidation of their endocrinological roles in the regulation of fundamental physiological processes. Graphical abstract: Image 1 Highlights: Bombyx CCHamide-1 and CCHamide-2 are specific endogenous ligands for BNGR-A15 and BNGR-A14, respectively. BNGR-A15 dually couples to Gs - and Gq -dependent pathways, while BNGR-A14 activates Gq -dependent cascades A disulfide bond is critical for CCHamides to activate their respective receptor in the physiological concentration range. BNGR-A14 might play multiple physiological roles, whereas BNGR-A15 is likely to function as a brain-gut peptide.