Drosophila GoLoco-protein Pins is a target of Galpha(o)-mediated G protein-coupled receptor signaling

Mol Biol Cell. 2009 Sep;20(17):3865-77. doi: 10.1091/mbc.e09-01-0021. Epub 2009 Jul 1.

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 Galpha(i/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 Galpha(o). We identify Pins GoLoco domain 1 as necessary and sufficient for this unusual interaction with Galpha(o)-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 Galpha(o)-mediated GPCR receptor signaling, e.g., in the context of the nervous system development, where Galpha(o) acts downstream from Frizzled and redundantly with Galpha(i) to control the asymmetry of cell divisions.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Sequence
  • Animals
  • Binding Sites
  • Cell Cycle Proteins
  • Drosophila Proteins / genetics
  • Drosophila Proteins / metabolism*
  • Drosophila melanogaster / anatomy & histology
  • Drosophila melanogaster / genetics
  • Drosophila melanogaster / metabolism
  • Frizzled Receptors / genetics
  • Frizzled Receptors / metabolism
  • GTP-Binding Protein alpha Subunits, Gi-Go / genetics
  • GTP-Binding Protein alpha Subunits, Gi-Go / metabolism*
  • GTPase-Activating Proteins / genetics
  • GTPase-Activating Proteins / metabolism
  • Guanine Nucleotide Dissociation Inhibitors / genetics
  • Guanine Nucleotide Dissociation Inhibitors / metabolism*
  • Guanosine Diphosphate / metabolism
  • Guanosine Triphosphate / metabolism
  • Humans
  • Lysine / metabolism
  • Molecular Sequence Data
  • Nerve Tissue Proteins / genetics
  • Nerve Tissue Proteins / metabolism
  • Receptors, G-Protein-Coupled / genetics
  • Receptors, G-Protein-Coupled / metabolism*
  • Sequence Alignment
  • Signal Transduction / physiology*
  • Two-Hybrid System Techniques

Substances

  • Cell Cycle Proteins
  • Drosophila Proteins
  • Frizzled Receptors
  • GTPase-Activating Proteins
  • Guanine Nucleotide Dissociation Inhibitors
  • LOCO protein, Drosophila
  • Nerve Tissue Proteins
  • Pins protein, Drosophila
  • Rapgap1 protein, Drosophila
  • Receptors, G-Protein-Coupled
  • fz protein, Drosophila
  • Guanosine Diphosphate
  • Guanosine Triphosphate
  • GTP-Binding Protein alpha Subunits, Gi-Go
  • Lysine