Making time for happyhour - May 21, 2009
Ulrike Heberlein at the University of California San Francisco and her colleagues have been studying the effects of alcohol on fruitflies for nearly 15 years. Their experiments have resulted in a slew of punchy Drosophila nomenclature stripped from the lexicon of lushes, like cheapdate, lightweight, and hangover , all for mutations and genes that control tolerance to various effects of alcohol. Their latest find is happyhour . Flies with a mutant version of this protein are less sensitive to alcohol’s sedating effects (Think Karen Allen in Raiders of the Lost Ark).
The happyhour protein is similar to a specific family of kinases (proteins that phosphorylate themselves or other proteins) which have been well described in mammals. Heberlein tells me that lead author, Ammon Corl, spent ages chasing a connection to the JNK and p38 pathways, which happyhour is predicted to target based on homology with human genes. The third suspect was the charm.
Through a series of genetic manipulations, they showed that the happyhour protein appears to work by inhibiting the activity of EGFR -- the extracellular growth factor receptor pathway -- which is conserved in flies and mammals and is a target of certain cancer drugs. One of these drugs, erlotinib, made flies and mice more sensitive to alcohol’s effects. Moreover it reduced alcohol consumption in rats that had become accustomed to a tipple. The authors suggest the results might point to therapeutic avenues for people with drinking problems.
Says Heberlein, “I’m pretty excited about this paper. It’s a complete story that goes from an unbiased screen in flies to a preclinical rat model.”
Image: detail from Happy Hour by aresauburn via Flickr under creative commons.
