Researchers led by Claudio Pikielny of Dartmouth Medical School recently discovered a link between a family of fruit fly proteins involved in mating behavior and the Tay-Sachs GM2-activator protein. The finding was published last month in The Journal of Biological Chemistry.
Drosophila melanogaster (fruit flies) engage in “a complex courtship behavior involving many precise steps,” Pikielny said in an e-mail interview. One component of the fruit fly courtship is the production of low volatility, lipid-like cuticular hydrocarbon pheromones. The mechanisms behind the detection of these pheromones however, are poorly understood.
It was only recently that Pikielny’s team discovered a family of proteins, the CheBs, that play a crucial role in how males detect female pheromones. Surprisingly, the CheB proteins involved in mating behavior were also found to be related to GM2-activating protein (GM2-AP), a human lipid binding protein whose absence results in the devastating Tay-Sachs disease. Tay-Sachs is a fatal genetic lipid storage disorder in which harmful quantities of a fatty substance called ganglioside GM2 build up in tissues and nerve cells in the brain.
“Our finding that CheBs are related to GM2-activator is very exciting to us for two reasons,” Pikielny said. “First, it suggests that CheBs and GM2-activator are involved in similar biochemical processes, and that our work may lead to a greater understanding of how the human protein works, and may even suggest therapeutical strategies for Tay-Sachs. Second, it suggests a mechanism for how the Drosophila CheB proteins contribute to the detection of pheromones.”
Drosophila pheromones are non-polar hydrocarbons and are thus insoluble in water, but soluble in non-polar lipids. It is known that GM2-activator binds neuronal lipids that resemble hydrocarbons, so the Pikielny team proposed that CheBs may therefore also bind to the hydrocarbon pheromones and thereby modulate their detection.
The loss of GM2-AP in Tay-Sachs disease prevents the degradation of GM2 gangliosides and results in neurodegeneration, and hence the function of CheBs in pheromone response may involve biochemical mechanisms critical for lipid metabolism in human neurons.
The Pikielny lab is currently continuing efforts to study the function of CheBs and their connection to GM2-AP.