| Title: | Gbeta promotes pheromone receptor polarization and yeast chemotropism by inhibiting receptor phosphorylation |
| Author(s): | Ismael A; Tian W; Waszczak N; Wang X; Cao Y; Suchkov D; Bar E; Metodiev MV; Liang J; Arkowitz RA; Stone DE; |
| Address: | "Department of Biological Sciences, University of Illinois at Chicago, Chicago, IL 60607, USA. Department of Bioengineering, University of Illinois at Chicago, Chicago, IL 60607, USA. School of Biological Sciences, University of Essex, Essex CO4 3SQ, UK. CNRS UMR7277/INSERM UMR1091/Universite Nice-Sophia Antipolis, Institute of Biology Valrose, 06108 Nice Cedex 2, France. Department of Biological Sciences, University of Illinois at Chicago, Chicago, IL 60607, USA. dstone@uic.edu" |
| DOI: | 10.1126/scisignal.aad4376 |
| ISSN/ISBN: | 1937-9145 (Electronic) 1945-0877 (Print) 1945-0877 (Linking) |
| Abstract: | "Gradient-directed cell migration (chemotaxis) and growth (chemotropism) are processes that are essential to the development and life cycles of all species. Cells use surface receptors to sense the shallow chemical gradients that elicit chemotaxis and chemotropism. Slight asymmetries in receptor activation are amplified by downstream signaling systems, which ultimately induce dynamic reorganization of the cytoskeleton. During the mating response of budding yeast, a model chemotropic system, the pheromone receptors on the plasma membrane polarize to the side of the cell closest to the stimulus. Although receptor polarization occurs before and independently of actin cable-dependent delivery of vesicles to the plasma membrane (directed secretion), it requires receptor internalization. Phosphorylation of pheromone receptors by yeast casein kinase 1 or 2 (Yck1/2) stimulates their internalization. We showed that the pheromone-responsive Gbetagamma dimer promotes the polarization of the pheromone receptor by interacting with Yck1/2 and locally inhibiting receptor phosphorylation. We also found that receptor phosphorylation is essential for chemotropism, independently of its role in inducing receptor internalization. A mathematical model supports the idea that the interaction between Gbetagamma and Yck1/2 results in differential phosphorylation and internalization of the pheromone receptor and accounts for its polarization before the initiation of directed secretion" |
| Keywords: | "Adaptor Proteins, Signal Transducing/genetics/metabolism Algorithms Casein Kinase I/genetics/metabolism Cell Membrane/metabolism Cell Polarity Chemotaxis Computer Simulation GTP-Binding Protein beta Subunits/chemistry/genetics/*metabolism GTP-Binding Prot;" |
| Notes: | "MedlineIsmael, Amber Tian, Wei Waszczak, Nicholas Wang, Xin Cao, Youfang Suchkov, Dmitry Bar, Eli Metodiev, Metodi V Liang, Jie Arkowitz, Robert A Stone, David E eng GM079804/GM/NIGMS NIH HHS/ R03 CA150131/CA/NCI NIH HHS/ R01 GM079804/GM/NIGMS NIH HHS/ 1R03CA150131/CA/NCI NIH HHS/ R01 CA187780/CA/NCI NIH HHS/ Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, Non-P.H.S. 2016/04/14 Sci Signal. 2016 Apr 12; 9(423):ra38. doi: 10.1126/scisignal.aad4376" |
