Center for Functional and Comparative Insect Genomics, Department of Biology, University of Copenhagen, DK-2100 Copenhagen, Denmark.
J Biol Chem. 2010 Apr 2;285(14):10736-47. doi: 10.1074/jbc.M109.045369. Epub 2010 Jan 12.
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.
神经肽及其 G 蛋白偶联受体 (GPCR) 在昆虫生理学中发挥着核心作用。昆虫神经肽的一个大家族是脂肪激活激素 (AKH)，它从昆虫脂肪体中动员脂质和碳水化合物。其他肽是心脏激素，它们在结构上与 AKH 相关，但代表不同的神经肽信号系统。我们之前从疟蚊冈比亚按蚊中克隆了一个孤儿 GPCR，该受体在结构上介于 AKH 和心脏激素 GPCR 之间。通过在细胞培养中的细胞中表达该受体的功能，我们现在已经确定了这种孤儿受体的配体是 pQVTFSRDWNAamide，这是一种结构上介于 AKH 和心脏激素之间的神经肽，因此我们将其命名为 ACP（AKH/心脏激素相关肽）。ACP 不能激活冈比亚按蚊 AKH 和心脏激素受体，反之亦然，AKH 和心脏激素也不能激活 ACP 受体，这表明 ACP/受体对是一个独立的、迄今为止未知的肽信号系统。由于 ACP 在结构上介于 AKH 和心脏激素之间，而 ACP 受体在 AKH 和心脏激素受体之间，这是一个突出的受体/配体共同进化的例子，可能源于受体和配体基因的复制，随后发生突变和进化选择，从而产生三个独立的激素系统。ACP 信号系统存在于蚊子冈比亚按蚊、埃及伊蚊和库蚊（双翅目）、家蚕（鳞翅目）、红面粉甲虫（鞘翅目）、寄生蜂天蚕（膜翅目）和臭虫（半翅目）中。然而，ACP 系统不存在于 12 种果蝇（双翅目）、蜜蜂（膜翅目）、豌豆蚜（半翅目）、体虱（虱目）和甲壳类动物水蚤（甲壳纲）中，表明它在节肢动物进化过程中已经丢失了多次。特别是，与脊椎动物相比，这种激素系统的频繁丢失在节肢动物中是独一无二的。
