Distinct Behavioral Responses to Ethanol Are Regulated by Alternate RhoGAP18B Isoforms

Adrian Rothenfluh, Robert J. Threlkeld, Roland J. Bainton, Linus T Y Tsai, Amy W. Lasek, Ulrike Heberlein

Research output: Contribution to journalArticle

92 Scopus citations

Abstract

In most organisms, low ethanol doses induce increased activity, while high doses are sedating. To investigate the underlying mechanisms, we isolated Drosophila mutants with altered ethanol responsiveness. Mutations in white rabbit (whir), disrupting RhoGAP18B, are strongly resistant to the sedating effects of ethanol. This resistance can be suppressed by reducing the levels of Rho1 or Rac, implicating these GTPases in the behavioral response to ethanol. Indeed, expression of constitutively active forms of Rho1 or Rac1 in adult flies results in ethanol resistance similar to that observed in whir mutants. The whir locus produces several transcripts, RA-RD, which are predicted to encode three distinct RhoGAPs that share only the GAP domain. The RC transcript mediates the sedating effects of ethanol, while the RA transcript regulates its stimulant effects. Thus, distinct RhoGAPs, encoded by the same gene, regulate different manifestations of acute ethanol intoxication.

Original languageEnglish (US)
Pages (from-to)199-211
Number of pages13
JournalCell
Volume127
Issue number1
DOIs
StatePublished - Oct 6 2006

    Fingerprint

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)

Cite this

Rothenfluh, A., Threlkeld, R. J., Bainton, R. J., Tsai, L. T. Y., Lasek, A. W., & Heberlein, U. (2006). Distinct Behavioral Responses to Ethanol Are Regulated by Alternate RhoGAP18B Isoforms. Cell, 127(1), 199-211. https://doi.org/10.1016/j.cell.2006.09.010