This report describes characterization of the fly alcohol response using the Drosophila gene Arf51F. Dmel\Arf51F is an ADP ribosylation factor GTP-binding protein; it is orthologous to ARF6 in human. Classical loss-of-function alleles, RNAi targeting constructs, alleles caused by insertional mutagenesis, and amorphic alleles created by targeted recombination have been generated for Dmel\Arf51F.
The human ARF6 gene has not been introduced into flies.
Animals homozygous for amorphic alleles of Dmel\Arf51F are sterile in both sexes; defects in cytokinesis during meiosis are observed. Animals homozygous for loss-of-function alleles are extremely sensitive to ethanol-induced sedation; pan-neuronal overexpression results in resistant phenotypes. A small number of genetic and physical interactions for Dmel\Arf51F have been described; see below and in the Arf51F gene report.
In the response to ethanol that determines the degree of resistance to ethanol-induced sedation, it is postulated that Arf51F protein is a downstream mediator of InR signaling (see 'alcohol, response to, insulin signaling pathway', FBhh0000692 and 'alcohol, response to, INSR-related', FBhh0000693).
[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]
Alcoholism is a multifactorial, genetically influenced disorder. [from MIM:103780; 2017.12.19]
The protein encoded by ARF6 is a GTP-binding protein that is localized to the plasma membrane and regulates vesicular trafficking, remodelling of membrane lipids, and signaling pathways that lead to actin remodeling. [Gene Cards, ARF6; 2018.01.08]
ARF6 encodes a small GTPase that regulates membrane trafficking between endosomes and the plasma membrane (Fang et al., 2006; pubmed:16737952). [from MIM:600464; 2018.01.08]
One to one: 1 human to 1 Drosophila.
High-scoring ortholog of human ARF6 (1 Drosophila to 1 human); Dmel\Arf51F shares 97% identity and 98% similarity with human ARF6.
