RRC ID 32427
Author Peru Y Colón de Portugal RL, Acevedo SF, Rodan AR, Chang LY, Eaton BA, Rothenfluh A.
Title Adult neuronal Arf6 controls ethanol-induced behavior with Arfaptin downstream of Rac1 and RhoGAP18B.
Journal J. Neurosci.
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.
Volume 32(49)
Pages 17706-13
Published 2012-12-5
DOI 10.1523/JNEUROSCI.1944-12.2012
PII 32/49/17706
PMID 23223291
PMC PMC3535434
MeSH ADP-Ribosylation Factors / genetics ADP-Ribosylation Factors / metabolism ADP-Ribosylation Factors / physiology* Animals Drosophila Proteins / genetics Drosophila Proteins / metabolism Drosophila Proteins / physiology* Ethanol / pharmacology* Female GTPase-Activating Proteins / genetics GTPase-Activating Proteins / metabolism GTPase-Activating Proteins / physiology* Hypnotics and Sedatives / pharmacology Intracellular Signaling Peptides and Proteins / metabolism* Male Mutant Proteins / genetics Mutant Proteins / metabolism Mutant Proteins / physiology Protein Isoforms / genetics Protein Isoforms / physiology Signal Transduction / genetics Signal Transduction / physiology rac1 GTP-Binding Protein / metabolism rac1 GTP-Binding Protein / physiology*
IF 5.971
Drosophila DGRC#104910