Drosophila GoLoco-Protein Pins is a target of G{alpha}o-mediated G Protein-coupled Receptor Signaling

Abstract

G protein-coupled receptors (GPCRs) transduce their signals through trimeric G proteins, inducing guanine nucleotide exchange on their Galpha-subunits; the resulting Galpha-GTP transmits the signal further inside the cell. GoLoco domains present in many proteins play important roles in multiple trimeric G protein-dependent activities, physically binding Galpha-subunits of the Galphai/o class. In most cases GoLoco binds exclusively to the GDP-loaded form of the Galpha-subunits. Here we demonstrate that the poly-GoLoco-containing protein Pins of Drosophila can bind to both GDP- and GTP-forms of Drosophila Galphao. We identify Pins GoLoco domain 1 as necessary and sufficient for this unusual interaction with Galphao-GTP. We further pinpoint a Lysine residue located centrally in this domain as necessary for the interaction. Our studies thus identify Drosophila Pins as a target of Galphao-mediated GPCR receptor signaling, e.g., in the context of the nervous system development, where Galphao acts downstream from Frizzled and redundantly with Galphai to control the asymmetry of cell divisions.