Mutations affecting the Drosophila G-protein–coupled receptor kinase Gprk2 were assessed for effects upon ethanol-induced behaviors. Multiple genetic reagents have been generated for Dmel\Gprk2, including amorphic mutations, RNAi-targeting constructs, overexpression constructs, and alleles caused by insertional mutagenesis.
Dmel\Gprk2 is orthologous to three human genes, GRK4, GRK5, and GRK6. Deleterious mutations in the three human genes affect different organs and regulatory processes. The human Hsap\GRK4 gene has been introduced into flies, but has not been characterized.
Animals homozygous for amorphic mutations of Dmel\Gprk2 exhibit an increase in alcohol‐induced hyperactivity, reduced sensitivity to the sedative effects of ethanol, and diminished rapid tolerance after a single intoxicating exposure. Knockdown of Gprk2 specifically in ellipsoid body neurons of the brain, effected by targeted RNAi, results in comparable phenotypes.
[updated Mar. 2021 by FlyBase; FBrf0222196]
Alcoholism can be defined as persistence of excessive drinking over a long period of time despite adverse health effects and disruption of social relations (Morozova et al., 2014; pubmed:24395673).
The 2013 Diagnostic and Statistical Manual of Mental Disorders (DSM) combined the two former categorizations of abnormal alcohol use (alcohol abuse and alcohol dependence) into one diagnosis: alcohol use disorder. The severity of an individual's AUD is broken into classifications: mild, moderate, or severe. "Alcoholism" is a non-medical term often used to describe a severe form of alcohol use disorder. (https://www.therecoveryvillage.com/recovery-blog/alcoholism-alcohol-use-disorder-whats-difference/)
Excessive alcohol consumption is associated with increased risk of different types of cancer, higher cardiovascular disease mortality, birth defects, liver diseases, and neuropsychiatric disorders (Morozova et al., 2014; pubmed:24395673).
Alcoholism is a multifactorial, genetically influenced disorder. [from MIM:103780; 2017.12.19]
G Protein-Coupled Receptor Kinase (GRK) 4, 5, and 6 are members of the guanine nucleotide-binding protein (G protein)-coupled receptor kinase subfamily of the Ser/Thr protein kinase family. The GRK proteins phosphorylate the activated forms of G protein-coupled receptors thus initiating their deactivation. [Gene Cards, GRK4, GRK5, GRK6; 210312]
Many to one: 3 human genes to 1 Drosophila gene; additional less closely related genes in both species.
Many to one: 3 human genes to 1 Drosophila gene; additional less closely related genes in both species.
Many to one: 3 human genes to 1 Drosophila gene; additional less closely related genes in both species.
High-scoring ortholog of human GRK5, GRK4, and GRK6 (1 Drosophila to 3 human); additional less closely related genes in both species. Dmel\Gprk2 shares 47-53% identity and 58-64% similarity with the human GRK5, GRK4, and GRK6 genes.
