This report describes characterization of the fly alcohol response using the Drosophila gene Akap200. Dmel\Akap200 encodes an A-kinase anchor protein; members of this protein family serve as anchoring proteins that mediate the subcellular compartmentation of protein kinase A (PKA) and protein kinase C (PKC). Akap200 is thought to be functionally related to mammalian AKAP12. RNAi targeting constructs and alleles caused by insertional mutagenesis have been generated for Dmel\Akap200.
The human AKAP12 gene has not been introduced into flies.
Animals homozygous for Akap200 loss-of-function mutations exhibit increased ethanol tolerance; some mutations also result in increased ethanol sensitivity. Physical and genetic interactions of Dmel\Akap200 have been described; see below and in the Akap200 gene report.
Work using this system indicates that Drosophila perineurial glia are critical for ethanol tolerance. In the fly model, PKA and calcium signaling appear to be coordinated by Akap200 in the perineurial glia to promote ethanol sensitivity and tolerance. Ethanol causes a structural remodeling of the actin cytoskeleton and perineurial membrane topology in an Akap200-dependent manner, without disrupting classical barrier functions.
See the human disease model 'alcohol, response to, RhoGAP-related' (FBhh0000691), which also supports a role for actin signaling and remodeling of the actin cytoskeleton in the response to ethanol.
[updated May 2019 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 A-kinase anchor proteins (AKAPs) are a group of structurally diverse proteins which have the common function of binding to the regulatory subunit of protein kinase A (PKA); they serve as anchoring proteins that mediate the subcellular compartmentation of protein kinase A (PKA) and protein kinase C (PKC). [from Gene Cards, AKAP12; 2019.05.03]
Mammalian AKAP12, functionally related to Akap200 (long isoform), is upregulated by ethanol and it shifts from the plasma membrane to the cytoplasm on calcium influx (FBrf0238081 and references cited therein).
