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General Information
Name
alcohol, response to, AKAP-related
FlyBase ID
FBhh0001013
OMIM
Overview

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]

Disease Summary Information
Parent Disease Summary: alcohol use disorder, susceptibility to (fly models overview)
Symptoms and phenotype
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 OMIM:103780; 2017.12.19]
Specific Disease Summary: alcohol, response to, AKAP-related
OMIM report
Human gene(s) implicated
Symptoms and phenotype
Genetics
Cellular phenotype and pathology
Molecular information
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).
External links
    Disease synonyms
    AUD susceptibility, AKAP-related
    Search term: alcohol use disorder
    Ortholog Information
    Human gene(s) in FlyBase
      Other mammalian ortholog(s) used
        D. melanogaster Gene Information (1)
        Gene Snapshot
        A kinase anchor protein 200 (Akap200) encodes a scaffolding protein that contributes to the spatial and temporal regulation of the Protein Kinase A holoenzyme. It regulates the Notch signaling and the organization of the actin cytoskeleton. [Date last reviewed: 2019-09-12]
        Gene Groups / Pathways
        Comments on ortholog(s)
        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 (53 groups)
        protein-protein
        Interacting group
        Assay
        References
        experimental knowledge based
        anti tag coimmunoprecipitation, Identification by mass spectrometry
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        anti tag coimmunoprecipitation, peptide massfingerprinting
        anti tag coimmunoprecipitation, peptide massfingerprinting
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        anti tag coimmunoprecipitation, western blot, anti tag western blot
        experimental knowledge based
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        anti tag coimmunoprecipitation, Identification by mass spectrometry
        experimental knowledge based
        anti bait coimmunoprecipitation, western blot
        experimental knowledge based
        experimental knowledge based
        experimental knowledge based
        anti tag coimmunoprecipitation, Identification by mass spectrometry
        experimental knowledge based
        experimental knowledge based
        experimental knowledge based
        experimental knowledge based
        anti tag coimmunoprecipitation, peptide massfingerprinting
        experimental knowledge based
        experimental knowledge based
        experimental knowledge based
        Alleles Reported to Model Human Disease (Disease Ontology) (0 alleles)
        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
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        Transgene
        Publicly Available Stocks
        Selected Drosophila transgenes
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        RNAi constructs available
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        Selected Drosophila classical alleles
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        References (3)