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.
Highlights
Using functional expression of the receptor in cells in cell culture, we have identified the ligand for this orphan receptor as being pQVTFSRDWNAamide, a neuropeptide that is structurally intermediate between Adipokinetic hormone (AKH) and corazonin and that we named AKH/ corazonin-related peptide (ACP) (AKH/corazonin-related peptide)
Adipokinetic hormone (AKH)3 is an insect neuropeptide produced by the corpora cardiaca, a neuroendocrine organ closely associated with the insect brain [1]
During high physical activities such as flight and intense locomotion, AKH is released into the circulation and transported to the fat body, where it binds to its G protein-coupled receptors (GPCRs) [2]
Summary
Zonin neuropeptides and the AKH and corazonin receptors are closely related, suggesting co-evolution of receptors and ligands in a process, where the ancestor receptor and neuropeptide genes have duplicated. The peptide increases heartbeat in cockroaches [10] and induces color change (darkening) associated with starvation, swarming, and migration in crowded locust populations [11], and in some insects, it is involved in the control of motor behavior associated with molting [12] These findings could perhaps mean that corazonin is involved in the management of stress situations, suggesting that AKHs and corazonins have specialized in the control of different aspects of stress or high physical activities, which would fit well with the receptor/ligand co-evolution hypothesis mentioned above. We show that the novel ACP/receptor couple is widely occurring in insects, suggesting that it is an important insect signaling system
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