title: Polarity mediates asymmetric trafficking of the Gbeta heterotrimeric G-protein subunit GPB-1 in C. elegans embryos.
abstract: Asymmetric cell division is an evolutionarily conserved process that gives rise to daughter cells with different fates. In one-cell stage C. elegans embryos, this process is accompanied by asymmetric spindle positioning, which is regulated by anterior-posterior (A-P) polarity cues and driven by force generators located at the cell membrane. These force generators comprise two Gα proteins, the coiled-coil protein LIN-5 and the GoLoco protein GPR-1/2. The distribution of GPR-1/2 at the cell membrane is asymmetric during mitosis, with more protein present on the posterior side, an asymmetry that is thought to be crucial for asymmetric spindle positioning. The mechanisms by which the distribution of components such as GPR-1/2 is regulated in time and space are incompletely understood. Here, we report that the distribution of the Gβ subunit GPB-1, a negative regulator of force generators, varies across the cell cycle, with levels at the cell membrane being lowest during mitosis. Furthermore, we uncover that GPB-1 trafficks through the endosomal network in a dynamin- and RAB-5-dependent manner, which is most apparent during mitosis. We find that GPB-1 trafficking is more pronounced on the anterior side and that this asymmetry is regulated by A-P polarity cues. In addition, we demonstrate that GPB-1 depletion results in the loss of GPR-1/2 asymmetry during mitosis. Overall, our results lead us to propose that modulation of Gβ trafficking plays a crucial role during the asymmetric division of one-cell stage C. elegans embryos.
authors.affiliation: Swiss Institute for Experimental Cancer Research (ISREC), School of Life Sciences, Swiss Federal Institute of Technology (EPFL), Lausanne CH-1015, Switzerland.
authors.forename: Kalyani
authors.initials: K
authors.lastname: Thyagarajan
authors.forename: Katayoun
authors.initials: K
authors.lastname: Afshar
authors.forename: Pierre
authors.initials: P
authors.lastname: Gönczy
mesh_terms: D000818:Animals; D017173:Caenorhabditis elegans / Q000196:embryology* / Q000235:genetics / Q000378:metabolism*; D029742:Caenorhabditis elegans Proteins / Q000235:genetics / Q000378:metabolism*; D002453:Cell Cycle / Q000235:genetics / Q000502:physiology; D016764:Cell Polarity / Q000235:genetics / Q000502:physiology*; D004625:Embryo, Nonmammalian / Q000378:metabolism*; D019084:Fluorescent Antibody Technique, Indirect; D044387:GTP-Binding Protein beta Subunits / Q000235:genetics / Q000378:metabolism*; D008938:Mitosis / Q000235:genetics / Q000502:physiology; D021381:Protein Transport / Q000235:genetics / Q000502:physiology
chemical_list: D029742:Caenorhabditis elegans Proteins; C475458:G protein regulator 1, C elegans; C475459:G protein regulator 2, C elegans; D044387:GTP-Binding Protein beta Subunits