View Program - 63rd Annual Drosophila Research Conference

The blood-brain barrier (BBB) is a highly selective cell layer that separates the nervous system and the circulating hemolymph. The BBB protects the brain from the contents of the circulating fluids that could impede neuronal function. Two layers of glial cells, Perineural Glia (PG) and Subperineural Glia (SPG) make up the BBB in Drosophila melanogaster which ensheathes the brain. We have previously shown that adult feminization of BBB cells in male Drosophila leads to reduced courtship levels.¹ In a microarray screen of isolated BBB cells we have identified several male-enriched transcripts.² One of them encodes the Dopamine-2 like receptor (D2R). We discovered that conditional knockdown of D2R in adult male Drosophila BBB decreases courtship levels. The D2R receptor is highly conserved and intriguingly, this receptor has been found to act via biased signaling (via G protein or arrestin) in mammals.³ We are interested in understanding the downstream signaling of D2R in the BBB of Drosophila that mediates the effect on courtship. We are examining biased signaling by the D2R receptor by mutagenizing D2R receptor residues that favor G protein or arrestin signaling, respectively. These constructs will be tested for their ability to rescue the D2R courtship defects when they are expressed in adult male Drosophila BBB. This will help us better understand how D2R contributes to the regulation of courtship in Drosophila.

References
1. Hoxha V, Lama C, Chang PL, Saurabh S, Patel N, Olate N, Dauwalder B. Sex-Specific Signaling in the Blood-Brain Barrier Is Required for Male Courtship in Drosophila. PLOS Genetics [Internet]. 2013 Jan
2. Lama C, Love CR, Le HN, Lama J, Dauwalder B. The nuclear receptor DHR3/Hr46 is required in the blood-brain barrier of mature males for courtship. bioRxiv [Internet]. 2021 Mar 30
3. Peterson SM, Pack TF, Wilkins AD, Urs NM, Urban DJ, Bass CE, Lichtarge O, Caron MG. Elucidation of G-protein and β-arrestin functional selectivity at the dopamine D2 receptor. Proceedings of the National Academy of Sciences of the United States of America [Internet]. 2015 Jun 2

Mechanisms of D2R signaling in the blood-brain barrier that regulates courtship in Drosophila melanogaster