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

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 mutants learned slower than wildtype controls, yet with additional training, they reached wildtype levels of performance. The w learning phenotype is also found in the w and w 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 mutants were resistant to this deficit. The w 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 learning. However, serotonin levels were not lower in the heads of the w mutants than in wildtype controls. There were also no significant differences found in synapse numbers within the w brain. We propose that the w learning defect may be due to inefficient biogenic amine signaling brought about by altered cholesterol homeostasis.