Receptor guanylyl cyclases in Inka cells targeted by eclosion hormone

Abstract

A signature of eclosion hormone (EH) action in insect ecdysis is elevation of cGMP in Inka cells, leading to massive release of ecdysis triggering hormone (ETH) and ecdysis initiation. Although this aspect of EH-induced signal transduction is well known, the receptor mediating this process has not been identified. Here, we describe a receptor guanylyl cyclase BdmGC-1 and its isoform BdmGC-1B in the Oriental fruit fly Bactrocera dorsalis that are activated by EH. The B form exhibits the conserved domains and putative N-glycosylation sites found in BdmGC-1, but possesses an additional 46-amino acid insertion in the extracellular domain and lacks the C-terminal tail of BdmGC-1. Combined immunolabeling and in situ hybridization reveal that BdmGC-1 is expressed in Inka cells. Heterologous expression of BdmGC-1 in HEK cells leads to robust increases in cGMP following exposure to low picomolar concentrations of EH. The B-isoform responds only to higher EH concentrations, suggesting different physiological roles of these cyclases. We propose that BdmGC-1 and BdmGC-1〉 are high-and low-affinity EH receptors, respectively.

Secretory competence in a gateway endocrine cell conferred by the nuclear receptor βFTZ-F1 enables stage-specific ecdysone responses throughout development in Drosophila

“…Pharmacological manipulations of Inka cells using various kinase and phosphatase inhibitors revealed Ca 2+ and cGMP-mediated pathways are likely to be involved in EH-induced secretion of ETH in M. sexta (Kingan, 2001). Identification of membrane bound guanylyl cyclases as EH receptors confirmed a cGMP-mediated transduction pathway for this neuropeptide also in flies (Chang et al, 2009). Elevation of cGMP in Inka cells at ecdysis thus provides evidence in support of EH-induced ETH release in Drosophila (Clark, 2004).…”

“…Elevation of cGMP in Inka cells at ecdysis thus provides evidence in support of EH-induced ETH release in Drosophila (Clark, 2004). Further support for neuropeptide regulated release of ETH comes from detection of corazonin and EH receptor expression in Inka cells of moths and flies (Chang et al, 2009; Kim et al, 2004; Zitnan and Adams, 2013). However, EH alone appears not to be essential for ETH secretion in Drosophila , since EH knockout flies complete ecdysis even in the absence of this neuropeptide and cGMP elevation in Inka cells.…”

Neural and Hormonal Control of Postecdysial Behaviors in Insects

“…However, Drosophila appears to be an anomaly in this regard and currently there is only negative evidence for regulation of bursicon-expressing neurons by EH. The recent identification of an EH receptor from Oriental fruitflies (7), which has an ortholog in Drosophila , may help resolve this issue. It is also possible that CCAP-expressing neurons that do not express bursicon regulate the activity of the bursicon-expressing neurons.…”

Large-Scale Combinatorial Deorphanization of Platynereis Neuropeptide GPCRs

“…These peptides can have neuromodulatory, neurotransmitter, or hormonal functions and can affect development, physiology, and the activity in neural circuits. The majority of neuropeptides signal by G-protein-coupled receptors (GPCRs), with some exceptions (Chang et al, 2009;Leung et al, 1987;Lowe et al, 1989;Rechler and Nissley, 1985). While the neuropeptide repertoire of an animal can be determined using a combination of sequencing and mass-spectrometry approaches (Collins et al, 2010;Conzelmann et al, 2013a;Dircksen et al, 2011;Hauser et al, 2010;Li et al, 2008;Xie et al, 2010), the determination of neuropeptide receptors is more difficult and is usually carried out using in vitro experiments with individual peptide-receptor pairs.…”