Discovery of a Novel Insect Neuropeptide Signaling System Closely Related to the Insect Adipokinetic Hormone and Corazonin Hormonal Systems

Abstract

Neuropeptides and their G protein-coupled receptors (GPCRs) play a central role in the physiology of insects. One large family of insect neuropeptides are the adipokinetic hormones (AKHs), which mobilize lipids and carbohydrates from the insect fat body. Other peptides are the corazonins that are structurally related to the AKHs but represent a different neuropeptide signaling system. We have previously cloned an orphan GPCR from the malaria mosquito Anopheles gambiae that was structurally intermediate between the A. gambiae AKH and corazonin GPCRs. Using functional expression of the receptor in cells in cell culture, we have now identified the ligand for this orphan receptor as being pQVTFSRDWNAamide, a neuropeptide that is structurally intermediate between AKH and corazonin and that we therefore named ACP (AKH/corazonin-related peptide). ACP does not activate the A. gambiae AKH and corazonin receptors and, vice versa, AKH and corazonin do not activate the ACP receptor, showing that the ACP/ receptor couple is an independent and so far unknown peptidergic signaling system. Because ACP is structurally intermediate between AKH and corazonin and the ACP receptor between the AKH and corazonin receptors, this is a prominent example of receptor/ligand co-evolution, probably originating from receptor and ligand gene duplications followed by mutations and evolutionary selection, thereby yielding three independent hormonal systems. The ACP signaling system occurs in the mosquitoes A. gambiae, Aedes aegypti, and Culex pipiens (Diptera), the silkworm Bombyx mori (Lepidoptera), the red flour beetle Tribolium castaneum (Coleoptera), the parasitic wasp Nasonia vitripennis (Hymenoptera), and the bug Rhodnius prolixus (Hemiptera). However, the ACP system is not present in 12 Drosophila species (Diptera), the honeybee Apis mellifera (Hymenoptera), the pea aphid Acyrthosiphon pisum (Hemiptera), the body louse Pediculus humanus (Phthiraptera), and the crustacean Daphnia pulex, indicating that it has been lost several times during arthropod evolution. In particular, this frequent loss of hormonal systems is unique for arthropods compared with vertebrates.

Evolution of gonadotropin-releasing hormone (GnRH) structure and its receptor

“…AKH is of similar length to GnRH and has a few key amino acids that match GnRH II. The same is true for several peptides related to AKH: corazonin, adipokinetic hormone/corazoninrelated peptides (ACP), and pigment-concentrating hormone (RPCH) Park et al, 2002;Hansen et al, 2010;Martin et al, 2011). Corazonin is even closer than AKH in sequence to GnRH II as they share pGlu 1 , Ser 4 , Gly 6 , Trp 7 , and amidation.…”

Identification and Functional Characterization of Two Orphan G-protein-coupled Receptors for Adipokinetic Hormones from Silkworm Bombyx mori

“…Our results clearly showed that both putative receptors were activated in intracellular cAMP accumulation, ERK1/2 phosphorylation, and receptor internalization and ␤-arrestin2 recruitment to membrane by AKH3 with high affinity, also by AKH1 and AKH2 with low affinity, but not by corazonin peptide, whereas Bombyx corazonin receptor was only activated by corazonin peptide but not by AKH1, AKH2, and AKH3. An orphan GPCR from the malaria mosquito A. gambiae was paired with the ligand AKH/corazonin-related peptide (ACP), a neuropeptide similar to Bombyx AKH3 that is structurally intermediate between AKH and corazonin and did not activate the Anopheles AKH and corazonin receptors, indicating that ACP/receptor couple is an independent and so far unknown neuropeptide signaling system (33). However, based on phylogenetic analysis and our current results, it is more likely that both the BNGR-A28 and -A29 receptors are specific for AKH3 and show cross-reaction with AKH1 and AKH2 to some degree but not with corazonin peptide.…”

G Protein-Coupled Receptors as Target Sites for Insecticide Discovery

“…In this chapter, we will cover recent progress made on identi fi cation, functional characterization and target screening of GPCRs for developing insecticides. Bonasio et al ( 2010 ) that are closely related to AKH and corazonin GPCRs (Hansen et al 2010 ) . Interestingly, ACP receptors are found in the mosquitoes ( Anopheles gambiae, Aedes aegypti , and Culex pipiens ) , the silkworm Bombyx mori , the red fl our beetle T. castaneum , the parasitoid wasp N. vitripennis , and the bug Rhodnius prolixus .…”

“…Interestingly, ACP receptors are found in the mosquitoes ( Anopheles gambiae, Aedes aegypti , and Culex pipiens ) , the silkworm Bombyx mori , the red fl our beetle T. castaneum , the parasitoid wasp N. vitripennis , and the bug Rhodnius prolixus . However, the ACP GPCR is not present in 12 Drosophila species, the honeybee A. mellifera , the pea aphid Acyrthosiphon pisum and the body louse Pediculus humanus (Hansen et al 2010 ) . Finally, proctolin receptors are missing from B. mori and A. mellifera (Roller et al 2008 ;Hummon et al 2006 ) .…”