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

Drosophila's white 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 white have several behavioral phenotypes that are independent of visual defects. This study characterizes a novel defect of white mutants in the acquisition of olfactory memory using the aversive olfactory conditioning paradigm. The w(1118) mutants learned slower than wildtype controls, yet with additional training, they reached wildtype levels of performance. The w(1118) learning phenotype is also found in the w(apricot) and w(coral) alleles, is dominant, and is rescued by genomic white and mini-white transgenes. Reducing dietary cholesterol strongly impaired olfactory learning for wildtype controls, while w(1118) mutants were resistant to this deficit. The w(1118) 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 white mutants significantly improved w(1118) learning. However, serotonin levels were not lower in the heads of the w(1118) mutants than in wildtype controls. There were also no significant differences found in synapse numbers within the w(1118) brain. We propose that the w(1118) learning defect may be due to inefficient biogenic amine signaling brought about by altered cholesterol homeostasis.

Automated summary

The study reveals a novel defect in olfactory memory acquisition in Drosophila white mutants, independent of visual defects. Mutants can reach wildtype performance levels with additional training. Dietary cholesterol intake and biogenic amine signaling may play a role in influencing the learning abilities of the mutants.