title: Enhancer of garnet/deltaAP-3 is a cryptic allele of the white gene and identifies the intracellular transport system for the white protein.
abstract: The white gene encodes an ABC-type transmembrane transporter that has a role in normal eye pigment deposition. In addition, overexpression in Drosophila leads to homosexual male courtship. Its human homologue has been implicated in cholesterol transport in macrophages and in mood disorders in human males. The garnet gene is a member of a group of other Drosophila eye colour genes that have been shown, or proposed, to function in intracellular protein transport. Recent molecular analysis indicates that it encodes the delta subunit of the AP-3 adaptin complex involved in vesicle transport from the trans-Golgi network to lysosomes and related organelles, such as pigment granules. This identification revealed a novel role for intracellular vesicular transport in Drosophila pigmentation. To further analyze this intracellular transport system, we examined the genetic interactions between garnet and a second site enhancer mutation, enhancer of garnet (e(g)). We show here that e(g) is a cryptic allele of the white gene. The white-garnet interaction is highly sensitive to the levels of both gene products but also shows some allele specificity for the white gene. The additive effect on pigmentation and the predicted protein products of these genes suggest that the garnet/AP-3 transport system ensures the correct intracellular localization of the white gene product. This model is further supported by the observation of homosexual male courtship behavior in garnet mutants, similar to that seen in flies overexpressing, and presumably mis-sorting, the white gene product. The w(e(g)) allele also enhances mutations in the subset of other eye-color genes with phenotypes similar to garnet. This observation supports a role for these genes in intracellular transport and leads to a model whereby incorrect sorting of the white gene product can explain the pigmentation phenotypes of an entire group of eye-color genes.
authors.affiliation: Department of Zoology, University of British Columbia, Vancouver, Canada. vlloyd@is.dal.ca
authors.forename: Vett K
authors.initials: VK
authors.lastname: Lloyd
authors.forename: D A R
authors.initials: DA
authors.lastname: Sinclair
authors.forename: M
authors.initials: M
authors.lastname: Alperyn
authors.forename: T A
authors.initials: TA
authors.lastname: Grigliatti
mesh_terms: D018528:ATP-Binding Cassette Transporters / Q000235:genetics; D033963:Adaptor Protein Complex 3; D033981:Adaptor Protein Complex delta Subunits; D000483:Alleles; D000818:Animals; D002875:Chromosomes; D003433:Crosses, Genetic; D004330:Drosophila / Q000235:genetics* / Q000378:metabolism; D029721:Drosophila Proteins / Q000235:genetics* / Q000378:metabolism; D004742:Enhancer Elements, Genetic; D005127:Eye Color / Q000235:genetics; D005136:Eye Proteins / Q000235:genetics* / Q000378:metabolism / Q000502:physiology; D005260:Female; D017353:Gene Deletion; D018628:Gene Dosage; D017344:Genes, Insect; D005838:Genotype; D019476:Insect Proteins / Q000235:genetics*; D008297:Male; D008954:Models, Biological; D010641:Phenotype; D021381:Protein Transport; D015183:Restriction Mapping; D012726:Sexual Behavior, Animal; D014157:Transcription Factors / Q000235:genetics*; D019076:Transgenes
chemical_list: C491904:AP3D1 protein, human; D018528:ATP-Binding Cassette Transporters; D033963:Adaptor Protein Complex 3; D033981:Adaptor Protein Complex delta Subunits; D029721:Drosophila Proteins; D005136:Eye Proteins; C406291:G protein, Drosophila; D019476:Insect Proteins; D014157:Transcription Factors; C059254:w protein, Drosophila