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General Information
Name
anxiety modulator(s), CCK-like receptors
FlyBase ID
FBhh0001008
Disease Ontology Term
Parent Disease
OMIM
Overview

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]

Disease Summary Information
Disease Summary: anxiety modulator(s), CCK-like receptors
OMIM report
Human gene(s) implicated
Symptoms and phenotype
Genetics
Cellular phenotype and pathology
Molecular information
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 OMIM:118445, 2019.04.23]
External links
Disease synonyms
Ortholog Information
Human gene(s) in FlyBase
    Other mammalian ortholog(s) used
      D. melanogaster Gene Information (2)
      Gene Snapshot
      Cholecystokinin-like receptor at 17D3 (CCKLR-17D3) encodes a class A transmembrane G protein coupled receptor that binds the neuropeptide ligand encoded by Dsk. It acts through the cAMP-PKA-CREB pathway and it is needed for the growth of neuromuscular junctions. It regulates food ingestion, satiety, hyperactivity, aggression and escape-related locomotion. [Date last reviewed: 2019-03-07]
      Cellular component (GO)
      Gene Groups / Pathways
      Comments on ortholog(s)
      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.
      Orthologs and Alignments from DRSC
      DIOPT - DRSC Integrative Ortholog Prediction Tool - Click the link below to search for orthologs in Humans
      Gene Snapshot
      Cholecystokinin-like receptor at 17D1 (CCKLR-17D1) encodes a neuropeptide receptor involved in locomotion and neuromuscular junction growth. [Date last reviewed: 2019-07-11]
      Gene Groups / Pathways
      Comments on ortholog(s)
      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.
      Orthologs and Alignments from DRSC
      DIOPT - DRSC Integrative Ortholog Prediction Tool - Click the link below to search for orthologs in Humans
      Synthetic Gene(s) Used (0)
      Summary of Physical Interactions (1 groups)
      protein-protein
      Interacting group
      Assay
      References
      Alleles Reported to Model Human Disease (Disease Ontology) (1 alleles)
      Models Based on Experimental Evidence ( 0 )
      Allele
      Disease
      Evidence
      References
      Modifiers Based on Experimental Evidence ( 1 )
      Allele
      Disease
      Interaction
      References
      Genetic Tools, Stocks and Reagents
      Sources of Stocks
      Contact lab of origin for a reagent not available from a public stock center.
      Bloomington Stock Center Disease Page
      Selected mammalian transgenes
      Allele
      Transgene
      Publicly Available Stocks
      Selected Drosophila transgenes
      Allele
      Transgene
      Publicly Available Stocks
      RNAi constructs available
      Allele
      Transgene
      Publicly Available Stocks
      Selected Drosophila classical alleles
      Allele
      Allele class
      Mutagen
      Publicly Available Stocks
      loss of function allele
      ethyl methanesulfonate
      References (4)