Animals homozygous for loss-of-function mutations of SNF4Aγ (aka loe or AMPKγ) exhibit age-dependent degeneration of the nervous system, dramatically visible as severe vacuolization of the adult brain. Dmel\SNF4Aγ encodes a subunit of the trimeric AMP-activated protein kinase (AMPK) complex; this enzyme is involved in cellular energy homeostasis. RNAi-targeting constructs and alleles caused by insertional mutagenesis have been generated for Dmel\SNF4Aγ.
Dmel\SNF4Aγ is orthologous to 3 human genes, PRKAG1, PRKAG2 and PRKAG3; PRKAG2 is implicated in several types of heart disease (MIM:602743). The human Hsap\PRKAG2 gene has been introduced into flies, but has not been characterized in the context of this disease model.
Several lines of evidence support the observation that the vacuolization and degeneration in SNF4Aγ mutants are confined to differentiated, probably synaptically active neurons, suggesting a role in maintaining neuronal integrity during adulthood. Genetic and physical interactions have been described for Dmel\SNF4Aγ; see below and in the SNF4Aγ gene report. Notable is genetic interactions with Dmel\Appl, β amyloid protein precursor-like (see human disease model 'Alzheimer disease 1' FBhh0000119).
[updated May 2019 by FlyBase; FBrf0222196]
AMP-activated protein kinase (AMPK) is a heterotrimeric protein composed of a catalytic alpha subunit, a noncatalytic beta subunit, and a noncatalytic regulatory gamma subunit. AMPK is an important energy-sensing enzyme that monitors cellular energy status and functions by inactivating key enzymes involved in regulating de novo biosynthesis of fatty acid and cholesterol. [Gene Cards, PRKAG2; 2019.05.06]
Many to one: 3 human to 1 Drosophila. The human genes are PRKAG1, PRKAG2 and PRKAG3.
Many to one: 3 human to 1 Drosophila. The human genes are PRKAG1, PRKAG2 and PRKAG3.
Many to one: 3 human to 1 Drosophila. The human genes are PRKAG1, PRKAG2 and PRKAG3.
Moderate-scoring ortholog of human PRKAG1, PRKAG2 and PRKAG3 (1 Drosophila to 3 human). Dmel\SNF4Aγ shares 39-57% identity and 53-71% similarity with the human genes (within the carboxy ligand binding and CBS repeat domains).
