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.

Name thesis:degree_name

Doctor of Philosophy

Level thesis:degree_level

Doctoral

Discipline thesis:degree_discipline

Cell and Molecular Biology

Grantor

University of Houston

Year dc:date.issued

2017

Author dc:creator

• Myers, Jennifer Laura 1966-

Advisor dc:contributor.advisor

• Dauwalder, Brigitte

Committee members dc:contributor.committeemember

• Roman, Gregg
• Ziburkus, Jokubas
• Wiernasz, Diane

• Drosophila
• ABC Transporter
• White gene
• Cholesterol
• 5-HT
• Acquisitions
• Memory
• Learning
• Olfactory conditioning

Statement dc:rights

• The author of this work is the copyright owner. UH Libraries and the Texas Digital Library have their permission to store and provide access to this work. Further transmission, reproduction, or presentation of this work is prohibited except with permission of the author(s).

Language dc:language.iso

eng

Handle dc:identifier.uri

http://hdl.handle.net/10657/2885

OAI identifier oai:identifier

oai:uh-ir.tdl.org:10657/2885