Drosophila GoLoco-protein Pins is a target of Galpha(o)-mediated G protein-coupled receptor signaling.
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.
Kopein
Damir
D
Department of Biology, University of Konstanz, D-78457 Konstanz, Germany.
Katanaev
Vladimir L
VL
D000595:Amino Acid Sequence; D000818:Animals; D001665:Binding Sites; D018797:Cell Cycle Proteins; D029721:Drosophila Proteins / Q000235:genetics / Q000378:metabolism*; D004331:Drosophila melanogaster / Q000033:anatomy & histology / Q000235:genetics / Q000378:metabolism; D051157:Frizzled Receptors / Q000235:genetics / Q000378:metabolism; D019206:GTP-Binding Protein alpha Subunits, Gi-Go / Q000235:genetics / Q000378:metabolism*; D020690:GTPase-Activating Proteins / Q000235:genetics / Q000378:metabolism; D020730:Guanine Nucleotide Dissociation Inhibitors / Q000235:genetics / Q000378:metabolism*; D006153:Guanosine Diphosphate / Q000378:metabolism; D006160:Guanosine Triphosphate / Q000378:metabolism; D006801:Humans; D008239:Lysine / Q000378:metabolism; D008969:Molecular Sequence Data; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000378:metabolism; D043562:Receptors, G-Protein-Coupled / Q000235:genetics / Q000378:metabolism*; D016415:Sequence Alignment; D015398:Signal Transduction / Q000502:physiology*; D020798:Two-Hybrid System Techniques
D018797:Cell Cycle Proteins; D029721:Drosophila Proteins; D051157:Frizzled Receptors; D020690:GTPase-Activating Proteins; D020730:Guanine Nucleotide Dissociation Inhibitors; C119015:LOCO protein, Drosophila; D009419:Nerve Tissue Proteins; C405164:Pins protein, Drosophila; C109224:Rapgap1 protein, Drosophila; D043562:Receptors, G-Protein-Coupled; C058784:fz protein, Drosophila; D006153:Guanosine Diphosphate; D006160:Guanosine Triphosphate; D019206:GTP-Binding Protein alpha Subunits, Gi-Go; D008239:Lysine