Royal jelly is a protein-, sugar-, lipid-, and mineral-containing food that is produced by worker bees of honeybee hives and that stimulates the development of a new queen bee (see Robinson for commentary). Kamakura noted that royal jelly lost its effectiveness after storage and isolated a protein, called royalactin, that was as effective as royal jelly in promoting the phenotypic changes associated with development of the queen—shortened developmental time, increased size of the adult, and increased ovary size. To explore the details of the pathways that might be responsible for these effects of royalactin, Kamakura fed royalactin to the fruit fly, Drosophila melanogaster, which does not have queens and workers, and found that the flies exhibited an increase in body weight and length, increased fecundity, and increased life span, which are all characteristics of the queen honeybee. Using flies with mutations or carrying RNA interference (RNAi) transgenes that disrupt various signaling pathways, Kamakura determined that royalactin signals through the epidermal growth factor receptor (EGFR) in the fat body. The effects on body size required EGFR-mediated signaling through PI3K-TOR-S6K (phosphatidylinositol 3-kinase to target of rapamycin to S6 kinase), a pathway known for stimulating protein synthesis and mediating growth. Activation of the mitogen-activated protein kinase (MAPK) pathway downstream of the EGFR was required for the shortened developmental time, and this was mediated by an increase in the production of the steroid hormone 20-hydroxyecdysone. EGFR signaling stimulated the production of juvenile hormone, transcription of the gene encoding yolk protein, and fecundity, but these effects were not affected by disruption of the MAPK or PI3K-TOR-S6K pathways, suggesting that there is another arm of EGFR signaling that functions in this process. How royalactin promotes longevity also remains an open question. Armed with this information from the fruit fly, Kamakura returned to the honeybee and showed by RNAi and selective pathway inhibition that EGFR and the pathways identified in the flies were involved in the increase in body size and shortening of developmental time associated with development of the honeybee queen in response to royalactin.
M. Kamakura, Royalactin induces queen differentiation in honeybees. Nature 473, 478–483 (2011). [PubMed]
G. E. Robinson, Royal aspirations. Nature 473, 454–455 (2011). [Online Journal]