Mutants of the white ABCG Transporter in Drosophila melanogaster Have Deficient Olfactory Learning and Cholesterol Homeostasis

• Published in: International journal of molecular sciences 2021-11, Vol.22 (23), p.12967
• Main Authors: Myers, Jennifer L, Porter, Maria, Narwold, Nicholas, Bhat, Krishna, Dauwalder, Brigitte, Roman, Gregg
• Format: Article
• Language: English
• Subjects: ABC transporters; Animals; ATP Binding Cassette Transporter, Subfamily G - genetics; ATP-Binding Cassette Transporters - genetics; Biosynthesis; Cholesterol; Cholesterol - analysis; Cholesterol - metabolism; Cholesterol, Dietary - analysis; Defects; Dopamine; Drosophila melanogaster - genetics; Drosophila melanogaster - physiology; Drosophila Proteins - genetics; Efflux; Esters; Eye Proteins - genetics; Fruit flies; Gene expression; Genotype & phenotype; Homeostasis; Homeostasis - genetics; Hypotheses; Insects; Learning - physiology; Lipid Metabolism - genetics; Memory - physiology; Mutants; Mutation - genetics; Nutrient deficiency; Olfactory discrimination learning; Phenotypes; Serotonin; Smell - genetics; Sterols; Synapses; Synapses - genetics; Transgenes; White gene
• ISSN: 1422-0067; 1661-6596; 1422-0067
• DOI: 10.3390/ijms222312967

's gene encodes an ATP-binding cassette G-subfamily (ABCG) half-transporter. White is closely related to mammalian ABCG family members that function in cholesterol efflux. Mutants of have several behavioral phenotypes that are independent of visual defects. This study characterizes a novel defect of mutants in the acquisition of olfactory memory using the aversive olfactory conditioning paradigm. The mutants learned slower than wildtype controls, yet with additional training, they reached wildtype levels of performance. The learning phenotype is also found in the and alleles, is dominant, and is rescued by genomic and mini- transgenes. Reducing dietary cholesterol strongly impaired olfactory learning for wildtype controls, while mutants were resistant to this deficit. The mutants displayed higher levels of cholesterol and cholesterol esters than wildtype under this low-cholesterol diet. Increasing levels of serotonin, dopamine, or both in the mutants significantly improved learning. However, serotonin levels were not lower in the heads of the mutants than in wildtype controls. There were also no significant differences found in synapse numbers within the brain. We propose that the learning defect may be due to inefficient biogenic amine signaling brought about by altered cholesterol homeostasis.