title: Adult neuronal Arf6 controls ethanol-induced behavior with Arfaptin downstream of Rac1 and RhoGAP18B.
abstract: Alcohol use disorders affect millions of individuals. However, the genes and signaling pathways involved in behavioral ethanol responses and addiction are poorly understood. Here we identify a conserved biochemical pathway that underlies the sedating effects of ethanol in Drosophila. Mutations in the Arf6 small GTPase signaling pathway cause hypersensitivity to ethanol-induced sedation. We show that Arf6 functions in the adult nervous system to control ethanol-induced behavior. We also find that the Drosophila Arfaptin protein directly binds to the activated forms of Arf6 and Rac1 GTPases, and mutants in Arfaptin also display ethanol sensitivity. Arf6 acts downstream of Rac1 and Arfaptin to regulate ethanol-induced behaviors, and we thus demonstrate that this conserved Rac1/Arfaptin/Arf6 pathway is a major mediator of ethanol-induced behavioral responses.
authors.affiliation: Department of Psychiatry and Program in Neuroscience, University of Texas Southwestern Medical Center at Dallas, Dallas, Texas 75390, USA.
authors.forename: Raniero L
authors.initials: RL
authors.lastname: Peru Y Colón de Portugal
authors.forename: Summer F
authors.initials: SF
authors.lastname: Acevedo
authors.forename: Aylin R
authors.initials: AR
authors.lastname: Rodan
authors.forename: Leo Y
authors.initials: LY
authors.lastname: Chang
authors.forename: Benjamin A
authors.initials: BA
authors.lastname: Eaton
authors.forename: Adrian
authors.initials: A
authors.lastname: Rothenfluh
mesh_terms: D000089982:ADP-Ribosylation Factor 6; D020727:ADP-Ribosylation Factors / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D000818:Animals; D029721:Drosophila Proteins / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D000431:Ethanol / Q000494:pharmacology*; D005260:Female; D020690:GTPase-Activating Proteins / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D006993:Hypnotics and Sedatives / Q000494:pharmacology; D047908:Intracellular Signaling Peptides and Proteins / Q000378:metabolism*; D008297:Male; D050505:Mutant Proteins / Q000235:genetics / Q000378:metabolism / Q000502:physiology; D020033:Protein Isoforms / Q000235:genetics / Q000502:physiology; D015398:Signal Transduction / Q000235:genetics / Q000502:physiology; D020830:rac1 GTP-Binding Protein / Q000378:metabolism / Q000502:physiology*
chemical_list: D000089982:ADP-Ribosylation Factor 6; C579633:Arfip protein, Drosophila; D029721:Drosophila Proteins; D020690:GTPase-Activating Proteins; D006993:Hypnotics and Sedatives; D047908:Intracellular Signaling Peptides and Proteins; D050505:Mutant Proteins; D020033:Protein Isoforms; C085379:rho GTPase-activating protein; D000431:Ethanol; D020727:ADP-Ribosylation Factors; D020830:rac1 GTP-Binding Protein