This report describes characterization of the fly alcohol response using the Drosophila gene S6k, which is postulated to act in the Drosophila insulin pathway. Classical loss-of-function alleles, RNAi-targeting constructs, and alleles caused by insertional mutagenesis have been generated for the S6k gene.
In human, there are two genes orthologous to Dmel\S6k, RPS6KB2 and RPS6KB1, which encode members of the ribosomal S6 kinase family of serine/threonine kinases. The human gene Hsap\RPS6KB1 has been introduced into flies; heterologous rescue has not been tested.
Severe loss-of-function mutations of Dmel\S6k are homozygous lethal in the larval stages; larvae exhibit neuroanatomy and neurophysiology defects. Extensive genetic interactions and a small number of physical interactions have been described for Dmel\S6k; see below and in the S6k gene report.
Pan-neuronal expression of a constitutively active mutation of S6k results in reduced sensitivity to ethanol-induced sedation. Sedation induced by ethanol correlates with the loss of S6k activity, as measured by loss of S6k phosphorylation (P-S6k). Activity of S6k is thus both a molecular marker and a behavioral determinant for ethanol-induced sedation.
[updated Jan. 2018 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]
The RPS6KB2 and RPS6KB1 genes encode members of the RSK (ribosomal S6 kinase) family of serine/threonine kinases, which phosphorylate the S6 ribosomal protein and eukaryotic translation initiation factor 4B (eIF4B). Phosphorylation of S6 leads to an increase in protein synthesis and cell proliferation. [from Gene Cards; RPS6KB2 and RPS6KB1; 2017.01.27]
Many to one (2 human to 1 Drosophila): the second orthologous gene in human is RPS6KB2; lower-scoring orthologs exist in both species.
Many to one (2 human to 1 Drosophila): the second orthologous gene in human is RPS6KB1; lower-scoring orthologs exist in both species.
High-scoring ortholog of human RPS6KB2 and RPS6KB1 (1 Drosophila to 2 human); lower-scoring orthologs exist in both species. Dmel\S6k shares 57-62% identity and 69-72% similarity with RPS6KB2 and RPS6KB1.
