Outside-in signaling--a brief review of GPCR signaling with a focus on the Drosophila GPCR family.

G-protein-coupled receptors (GPCRs) are the largest family of receptors in many organisms, including worms, mice and humans. GPCRs are seven-transmembrane pass proteins that are activated by binding a stimulus (or ligand) in the extracellular space and then transduce that information to the inside of the cell through conformational changes. The conformational changes activate heterotrimeric G-proteins, which execute the downstream signaling pathways through the recruitment and activation of cellular enzymes. The highly specific ligand-GPCR interaction prompts an efficient cellular response, which is vital for the health of the cell and organism. In this Commentary, we review general features of GPCR signaling and then focus on the Drosophila GPCRs, which are not as well-characterized as their worm and mammalian counterparts. We discuss findings that the Drosophila odorant and gustatory receptors are not bona fide GPCRs as is the case for their mammalian counterparts. We also present here a phylogenetic analysis of the bona fide Drosophila GPCRs that suggest potential roles for several family members. Finally, we discuss recently discovered roles of GPCRs in Drosophila embryogenesis, a field we expect will uncover many previously unappreciated functions for GPCRs.