The Drosophila gene scarlet (st) encodes a transmembrane ATP-binding cassette (ABC) transporter responsible for the transport of metabolites such as 3-hydroxykynurenine (3-HK). It is one of multiple genes in Drosophila orthologous to the G subfamily of ABC transporters (ABCG) in human.
In a screen for mutations associated with degeneration of dopaminergic neurons in the adult brain, several new alleles of the classical eye color gene scarlet (st) were isolated. Animals homozygous for the original st1 mutation were assessed; they also exhibit loss of dopaminergic neurons. In addition, progressive locomotor defects and reduced lifespan are observed; these phenotypes are more severe in hemizygous animals.
None of the human ABCG genes has been introduced into flies. A large number of classical loss-of-function alleles, RNAi-targeting constructs, and alleles caused by insertional mutagenesis have been generated for st.
Manipulation of the kynurenine pathway, either genetically (using mutations of the cn gene) or pharmacologically (using KYNA-supplemented food) ameliorates the st dopaminergic neuron loss phenotype. In a Drosophila model of Parkinson disease 1 (FBhh0000006), neural expression of human α-synuclein (Hsap\SNCA) results in loss of dopaminergic neurons and progressive locomotor defects; overexpression of wild-type st in addition to Hsap\SNCA prevents both phenotypes. Mutations in other genes involved in the kynurenine pathway have been observed to ameliorate or exacerbate neurodegenerative phenotypes (FBrf0234273, FBrf0214220).
[updated Mar. 2019 by FlyBase; FBrf0222196]
Scarlet (st) encodes an ABC transporter responsible for the transport of metabolites such as 3-hydroxykynurenine (3-HK) across the membrane of pigment granules (FBrf0240062 and references cited therein).
Members of the ATP binding cassette subfamily G (ABCG) consist of a single ABC cassette in the amino terminal followed by six putative transmembrane domains; to become functionally active, they form homo- or obligate heterodimers (Kusuhara and Sugiyama, 2007; pubmed:16983557).
HGNC gene group ATP binding cassette subfamily G (ABCG) has 5 members (https://www.genenames.org/data/genegroup/#!/group/811).
Many to many: 5 human to many Drosophila. The human genes are ABCG5, ABCG8, ABCG2, ABCG4, ABCG1.
Many to many: 5 human to many Drosophila. The human genes are ABCG5, ABCG8, ABCG2, ABCG4, ABCG1.
Many to many: 5 human to many Drosophila. The human genes are ABCG5, ABCG8, ABCG2, ABCG4, ABCG1.
Many to many: 5 human to many Drosophila. The human genes are ABCG5, ABCG8, ABCG2, ABCG4, ABCG1.
Many to many: 5 human to many Drosophila. The human genes are ABCG5, ABCG8, ABCG2, ABCG4, ABCG1.
Low-scoring ortholog of human ABCG5, ABCG8, ABCG2, ABCG4, and ABCG1 genes (many Drosophila to 5 human). Dmel\st shares 28-31% identity and 45-50% similarity with the human genes. There are over a dozen genes in the ABCG transporter family in Drosophila (see Gene Group report FBgg0000540).
