@article{highfill_baker_stevens_anholt_mackay_2019, title={Genetics of cocaine and methamphetamine consumption and preference in Drosophila melanogaster}, volume={15}, ISSN={["1553-7404"]}, DOI={10.1371/journal.pgen.1007834}, abstractNote={Illicit use of psychostimulants, such as cocaine and methamphetamine, constitutes a significant public health problem. Whereas neural mechanisms that mediate the effects of these drugs are well-characterized, genetic factors that account for individual variation in susceptibility to substance abuse and addiction remain largely unknown. Drosophila melanogaster can serve as a translational model for studies on substance abuse, since flies have a dopamine transporter that can bind cocaine and methamphetamine, and exposure to these compounds elicits effects similar to those observed in people, suggesting conserved evolutionary mechanisms underlying drug responses. Here, we used the D. melanogaster Genetic Reference Panel to investigate the genetic basis for variation in psychostimulant drug consumption, to determine whether similar or distinct genetic networks underlie variation in consumption of cocaine and methamphetamine, and to assess the extent of sexual dimorphism and effect of genetic context on variation in voluntary drug consumption. Quantification of natural genetic variation in voluntary consumption, preference, and change in consumption and preference over time for cocaine and methamphetamine uncovered significant genetic variation for all traits, including sex-, exposure- and drug-specific genetic variation. Genome wide association analyses identified both shared and drug-specific candidate genes, which could be integrated in genetic interaction networks. We assessed the effects of ubiquitous RNA interference (RNAi) on consumption behaviors for 34 candidate genes: all affected at least one behavior. Finally, we utilized RNAi knockdown in the nervous system to implicate dopaminergic neurons and the mushroom bodies as part of the neural circuitry underlying experience-dependent development of drug preference.}, number={5}, journal={PLOS GENETICS}, author={Highfill, Chad A. and Baker, Brandon M. and Stevens, Stephenie D. and Anholt, Robert R. H. and Mackay, Trudy F. C.}, year={2019}, month={May} }
 @article{makaraci_cruz_mcdermott_nguyen_highfill_kim_2019, title={Yeast dynamin and Ypt6 function in parallel for the endosome-to-Golgi retrieval of Snc1}, volume={43}, ISSN={["1095-8355"]}, DOI={10.1002/cbin.11042}, abstractNote={AbstractProtein recycling is an important cellular process required for cell homeostasis. Results from prior studies have shown that vacuolar sorting protein‐1 (Vps1), a dynamin homolog in yeast, is implicated in protein recycling from the endosome to the trans‐Golgi Network (TGN). However, the function of Vps1 in relation to Ypt6, a master GTPase in the recycling pathway, remains unknown. The present study reveals that Vps1 physically interacts with Ypt6 if at least one of them is full‐length. We found that overexpression of full‐length Vps1, but not GTP hydrolysis‐defective Vps1 mutants, is sufficient to rescue abnormal phenotypes of Snc1 distribution provoked by the loss of Ypt6, and vice versa. This suggests that Vps1 and Ypt6 function in parallel pathways instead of in a sequential pathway and that GTP binding/hydrolysis of Vps1 is required for proper traffic of Snc1 toward the TGN. Additionally, we identified two novel Vps1‐binding partners, Vti1 and Snc2, which function for the endosome‐derived vesicle fusion at the TGN. Taken together, the present study demonstrates that Vps1 plays a role in later stages of the endosome‐to‐TGN traffic.}, number={10}, journal={CELL BIOLOGY INTERNATIONAL}, author={Makaraci, Pelin and Cruz, Marie Delgado and McDermott, Hyoeun and Nguyen, Vy and Highfill, Chad and Kim, Kyoungtae}, year={2019}, month={Oct}, pages={1137–1151} }