Domain-specific control of germ cell polarity and migration by multifunction Tre1 GPCR

The migration of primordial germ cells (PGCs) from their place of origin to the embryonic gonad is an essential reproductive feature in many animal species. In Drosophila melanogaster, a single G protein-coupled receptor, Trapped in endoderm 1 (Tre1), mediates germ cell polarization at the onset of active migration and directs subsequent migration of PGCs through the midgut primordium. How these different aspects of cell behavior are coordinated through a single receptor is not known. We demonstrate that two highly conserved domains, the E/N/DRY and NPxxY motifs, have overlapping and unique functions in Tre1. The Tre1-NRY domain via G protein signaling is required for reading and responding to guidance and survival cues controlled by the lipid phosphate phosphatases Wunen and Wunen2. In contrast, the Tre1-NPIIY domain has a separate role in Rho1- and E-cadherin-mediated polarization at the initiation stage independent of G protein signaling. We propose that this bifurcation of the Tre1 G protein-coupled receptor signaling response via G protein-dependent and independent branches enables distinct spatiotemporal regulation of germ cell migration.