Fly orthologs of candidate anxiety genes found at quantitative trait loci (QTLs) identified from a mouse genetic experiment were screened using the fly wall-following assay (WAFO, see FBhh0001005). Of 17 fly genes test, 4 exhibited alterations in the WAFO assay, including Dmel\CCKLR-17D1 and Dmel\CCKLR-17D3. Knockdown of either gene resulted in reduced WAFO (interpreted as decreased anxiety). These 2 paralogous genes are orthologous to a pair of human genes, CCKAR and CCKBR. The genes encode G-protein-coupled receptors that bind neuropeptide ligands, in the case of human the CCK neuropeptide. In mammals, type B receptors are thought to regulate anxiety, arousal, neuroleptic activity, and opiate-induced analgesia.
Neither human CCK receptor gene has been introduced into flies.
RNAi-targeting constructs and alleles caused by insertional mutagenesis have been generated for both Dmel\CCKLR-17D1 and Dmel\CCKLR-17D3. A small number of genetic and physical interactions have been described for Dmel\CCKLR-17D1. See below and in the CCKLR-17D1 and CCKLR-17D3 gene reports.
[updated Apr. 2019 by FlyBase; FBrf0222196]
CCKAR encodes a G-protein coupled receptor that binds non-sulfated members of the cholecystokinin (CCK) family of peptide hormones. This receptor is a major physiologic mediator of pancreatic enzyme secretion and smooth muscle contraction of the gallbladder and stomach. [Gene Cards, CCKAR; 2019.04.23]
CCKBR gene encodes a G-protein coupled receptor for gastrin and cholecystokinin (CCK), regulatory peptides of the brain and gastrointestinal tract. This protein is a type B gastrin receptor, which has a high affinity for both sulfated and nonsulfated CCK analogs. [Gene Cards, CCKBR; 2019.04.23]
The cholecystokinin (CCK) family of peptides and their receptors are widely distributed throughout the central nervous system and gastrointestinal tract. The receptors can be divided into 2 subtypes on the basis of their affinity for nonsulfated analogs of CCK. In the CNS, type B receptors regulate anxiety, arousal, neuroleptic activity, and opiate-induced analgesia. [from MIM:118445, 2019.04.23]
Moderate-scoring ortholog of human CCKAR and CCKBR (2 Drosophila to 2 human); Dmel\CCKLR-17D3 shares 33-35% identity and 47-49% similarity with the human genes.
Moderate-scoring ortholog of human CCKAR and CCKBR (2 Drosophila to 2 human); Dmel\CCKLR-17D1 shares 30-31% identity and 46-49% similarity with the human genes.
