moody encodes two GPCRs that regulate cocaine behaviors and blood-brain barrier permeability in Drosophila.
We identified moody in a genetic screen for Drosophila mutants with altered cocaine sensitivity. Hypomorphic mutations in moody cause an increased sensitivity to cocaine and nicotine exposure. In contrast, sensitivity to the acute intoxicating effects of ethanol is reduced. The moody locus encodes two novel GPCRs, Moody-alpha and Moody-beta. While identical in their membrane-spanning domains, the two Moody proteins differ in their long carboxy-terminal domains, which are generated by use of alternative reading frames. Both Moody forms are required for normal cocaine sensitivity, suggesting that they carry out distinct but complementary functions. Moody-alpha and Moody-beta are coexpressed in surface glia that surround the nervous system, where they are actively required to maintain the integrity of the blood-brain barrier in the adult fly. We propose that a Moody-mediated signaling pathway functions in glia to regulate nervous system insulation and drug-related behaviors.
Bainton
Roland J
RJ
Department of Anesthesia, University of California, San Francisco, CA 94143, USA.
Tsai
Linus T-Y
LT
Schwabe
Tina
T
DeSalvo
Michael
M
Gaul
Ulrike
U
Heberlein
Ulrike
U
D017398:Alternative Splicing / Q000235:genetics; D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects / Q000502:physiology; D001812:Blood-Brain Barrier / Q000187:drug effects / Q000378:metabolism*; D001921:Brain / Q000187:drug effects / Q000378:metabolism*; D003042:Cocaine / Q000494:pharmacology; D019970:Cocaine-Related Disorders / Q000235:genetics / Q000378:metabolism; D004195:Disease Models, Animal; D018765:Dopamine Uptake Inhibitors / Q000494:pharmacology; D029721:Drosophila Proteins / Q000235:genetics / Q000302:isolation & purification / Q000378:metabolism*; D004331:Drosophila melanogaster / Q000187:drug effects / Q000235:genetics / Q000378:metabolism*; D004361:Drug Tolerance / Q000235:genetics; D008297:Male; D009043:Motor Activity / Q000187:drug effects / Q000502:physiology; D009457:Neuroglia / Q000166:cytology / Q000378:metabolism; D009538:Nicotine / Q000494:pharmacology; D017434:Protein Structure, Tertiary / Q000235:genetics; D043562:Receptors, G-Protein-Coupled / Q000235:genetics / Q000302:isolation & purification / Q000378:metabolism*; D019966:Substance-Related Disorders / Q000235:genetics
D018765:Dopamine Uptake Inhibitors; D029721:Drosophila Proteins; D043562:Receptors, G-Protein-Coupled; C542235:moody protein, Drosophila; D009538:Nicotine; D003042:Cocaine