This report describes characterization of the fly alcohol response using the Drosophila gene Cp1. Dmel\Cp1 encodes a member of the cysteine cathepsin protease family. There are multiple members of this family in both Drosophila and human; the mostly closed related human genes are CTSV and CTSL. RNAi targeting constructs and alleles caused by insertional mutagenesis have been generated for Dmel\Cp1.
A UAS construct of the human Hsap\CTSV gene has been introduced into flies, but has not been characterized.
Animals homozygous for loss-of-function mutations of Dmel\Cp1 are viable; in some cases, females are sterile. In adult flies, RNAi-effected knockdown of Dmel\Cp1 in glia increases alcohol sedation in response to acute administration of alcohol; this effect is specific to cortex glia and adulthood. Genetic and physical interactions of Dmel\Cp1 have been described; see below and in the Cp1 gene report.
[updated Feb. 2020 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]
Cathepsins comprise a highly conserved protease family distinguished by their structure, catalytic mechanism, and substrate specificities. Most members of this family function primarily in lysosomes, becoming activated at the low pH found in lysosomes (https://www.genenames.org/data/genegroup/#!/group/470).
Cysteine cathepsins are optimally active in a slightly acidic pH and are mostly unstable at neutral pH. The view of cysteine cathepsins as exclusively lysosomal proteases is changing as there is now clear evidence of their localization in other cellular compartments. (Turk et al., 2012; pubmed:22024571).
Many to many: multiple related genes in both species.
Many to many: multiple related genes in both species.
Moderate- to high-scoring ortholog of human CTSV and CTSL; multiple related genes in both species. Dmel\Cp1 shares 51-52% identity and 67% similarity with CTSV and CTSL.
