title: Heterotrimeric G-protein shuttling via Gip1 extends the dynamic range of eukaryotic chemotaxis.
abstract: Chemotactic eukaryote cells can sense chemical gradients over a wide range of concentrations via heterotrimeric G-protein signaling; however, the underlying wide-range sensing mechanisms are only partially understood. Here we report that a novel regulator of G proteins, G protein-interacting protein 1 (Gip1), is essential for extending the chemotactic range ofDictyosteliumcells. Genetic disruption of Gip1 caused severe defects in gradient sensing and directed cell migration at high but not low concentrations of chemoattractant. Also, Gip1 was found to bind and sequester G proteins in cytosolic pools. Receptor activation induced G-protein translocation to the plasma membrane from the cytosol in a Gip1-dependent manner, causing a biased redistribution of G protein on the membrane along a chemoattractant gradient. These findings suggest that Gip1 regulates G-protein shuttling between the cytosol and the membrane to ensure the availability and biased redistribution of G protein on the membrane for receptor-mediated chemotactic signaling. This mechanism offers an explanation for the wide-range sensing seen in eukaryotic chemotaxis.
authors.affiliation: Laboratory for Cell Signaling Dynamics, Quantitative Biology Center (QBiC), RIKEN, Suita, Osaka, 565-0874, Japan; Laboratory for Single Molecular Biology, Department of Biological Sciences, Graduate School of Science, Osaka University, Toyonaka, Osaka, 560-0043, Japan.
authors.forename: Yoichiro
authors.initials: Y
authors.lastname: Kamimura
authors.affiliation: Laboratory for Cell Signaling Dynamics, Quantitative Biology Center (QBiC), RIKEN, Suita, Osaka, 565-0874, Japan; Laboratory for Single Molecular Biology, Department of Biological Sciences, Graduate School of Science, Osaka University, Toyonaka, Osaka, 560-0043, Japan.
authors.forename: Yukihiro
authors.initials: Y
authors.lastname: Miyanaga
authors.affiliation: Laboratory for Cell Signaling Dynamics, Quantitative Biology Center (QBiC), RIKEN, Suita, Osaka, 565-0874, Japan; Laboratory for Single Molecular Biology, Department of Biological Sciences, Graduate School of Science, Osaka University, Toyonaka, Osaka, 560-0043, Japan masahiroueda@fbs.osaka-u.ac.jp.
authors.forename: Masahiro
authors.initials: M
authors.lastname: Ueda
mesh_terms: D002462:Cell Membrane / Q000235:genetics / Q000378:metabolism*; D002633:Chemotaxis / Q000502:physiology*; D004023:Dictyostelium / Q000235:genetics / Q000378:metabolism*; D020555:GTP-Binding Protein Regulators / Q000235:genetics / Q000378:metabolism*; D020962:Heterotrimeric GTP-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction / Q000502:physiology*
chemical_list: D020555:GTP-Binding Protein Regulators; D020962:Heterotrimeric GTP-Binding Proteins
keywords: dynamic range extension; eukaryotic chemotaxis; gradient sensing; heterotrimeric G protein