Adult neuronal Arf6 controls ethanol-induced behavior with Arfaptin downstream of Rac1 and RhoGAP18B

Raniero L. Peru y Colón de Portugal, Summer F. Acevedo, Aylin R. Rodan, Leo Y. Chang, Benjamin A. Eaton, Adrian Rothenfluh

Research output: Contribution to journalArticlepeer-review

27 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)17706-17713
Number of pages8
JournalJournal of Neuroscience
Volume32
Issue number49
DOIs
StatePublished - Dec 5 2012

ASJC Scopus subject areas

  • General Neuroscience

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