Mutants of Drosophila Melanogaster's ABC Transporter, White, Have Altered Cholesterol-Mediated Acquisition of Memory that is Moderated with 5-HT

Since the discovery of Drosophila melanogaster’s white gene over 100 years ago, white has become an important genetic tool in Drosophila research. The distinct white-eyed phenotype has allowed researchers to do seminal work on heredity, gene regulation, and whole organism studies with transgenic modification. The white gene encodes an ATP binding cassette G-subfamily (ABCG) half transporter for the precursors of eye pigments and possibly biogenic amines, 5-hydroxytryptamine (5-HT) and dopamine that are critical for olfactory learning and memory in Drosophila. ABCG transporters are also known for their roles in lipid transport and homeostasis. In recent years, several behavioral differences in learning and memory have been found in white mutants that are independent of eye color and associated with 5-HT. This study characterizes a novel defect in the acquisition of olfactory memory of white mutants using the well-established classical conditioning paradigm. Classical olfactory conditioning pairs odors to shock and requires the fly to discriminate between shock paired odors and unpaired odors. The White transporter was found to be both necessary and sufficient for wild-type acquisition. 5-HTP feeding can modulate acquisition. Low 5-HT in the heads of flies, however, is not sufficient to simulate the poor acquisition seen in white mutants. This is in agreement with the normal acquisition seen in mutants of known white binding partners, scarlet1 and brown1, and high levels of 5-HT found in the heads of white1118 mutants using HPLC. Two other Drosophila ABCG mutants (CG3164MI and CG17646MI) with putative roles in cholesterol homeostasis also have poor acquisition both as homozygotes and as double heterozygotes with white1118. Mutant alleles of these ABCGs and white1118 are all partially dominant to wild-type alleles. The white1118 mutants have better acquisition with low levels of dietary cholesterol compared to high levels (0.01 mg/ml) in contrast to Canton-S wild-type flies that have better acquisition with high cholesterol feedings. Fly mass for females and males was unchanged between genotypes and cholesterol treatment. Taken together, these data suggest that the white gene has altered cholesterol homeostasis that mediates early acquisition of memory and is sensitive to 5-HT signaling.Biology and Biochemistry, Department o