“Chemistry” is the metaphor often used to describe the spark of human sexual attraction. But people aside, science knows that in many creatures, mating literally is ignited by powerful chemical signals known as sex pheromones—hormones released by one animal that prompt sexual behavior in another.
Researchers have discovered thousands of pheromones, mostly in insects. In the late 1990s, UTMB scientists, led by Sherry Painter and Gregg Nagle, were the first to identify a waterborne sex pheromone of an invertebrate—a protein they named “attractin.” Different varieties of attractin are produced by members of the genus Aplysia—commonly called sea slugs—along with other ingredients of a pheromone “bouquet” dubbed “enticin,” “temptin,” and “seductin.” Painter and Nagle discovered that attractins have an incredibly powerful effect on the hand-sized, nearly blind creatures, long used for basic research on neural and hormonal intercellular communication: just a teaspoonful of attractin in a swimming pool-sized tank can send sea slugs into a mating frenzy.
Subsequently, Painter, Nagle, and postdoctoral fellow Scott Cummins teamed up with UTMB structural biologists Catherine Schein and Werner Braun, and collaborators including Ravi Garimella and Yuan Xu, both experts in using nuclear magnetic resonance (NMR), to determine the three-dimensional shapes of complex proteins. Their biochemical, behavioral, and NMR studies of the different varieties of attractin and other ingredients of the bouquet of sex pheromones produced by five different species of Aplysia have taken years. That’s largely because they had to schedule many of their experiments around the annual sea slug mating season. But the results—published this year in the prestigious Proceedings of the National Academy of Sciences, The Journal of Biological Chemistry, and Biochemistry—were worth the wait.
The attractins, the researchers discovered, have a property that makes them different from other sex pheromones—one that explains the mysterious tendency of mating sea slugs to congregate in large mixed-species groups that Aplysia researchers call “brothels.” While most sex pheromones affect only the species that produces them, different sex pheromones made by different species of Aplysia induce mating behavior across species lines. Attractin from the Pacific Ocean sea slug Aplysia californica, for example, stimulates mating behavior in Aplysia brasiliana, a species found off the Texas coast.
This “promiscuity of the signal,” as Nagle calls it, is what gave Painter the idea that the different animals were all releasing similar proteins. To verify this hunch, Nagle, Cummins, and Painter determined the pheromones’ amino acid sequences and found that the chemical building blocks that made up each protein were assembled in a strikingly similar order. Moreover, the line-up of amino acids in one critical part of the three-dimensional NMR structure that Schein and Braun’s team produced for Aplysia californica attractin matched sequences found in the other four attractins.
The shape of this particular piece of the protein matched something else as well: a well-studied pheromone used by a single-celled organism, the protozoan Euplotes. That pheromone is thought to be similar to the mammalian immune-signaling cytokine interleukin-2, receptors of which it can bind to. “Evolutionarily speaking, the Aplysia are very old animals, hundreds of millions of years old,” Nagle says. “Water-borne pheromones may be ancestors of cytokines in higher organisms.” If so, attractin studies may have implications that go far beyond the sex lives of sea slugs. They could provide clues to the roots and structure of the intercellular communications systems most crucial to human health. —Jim Kelly