title: LET-99 opposes Galpha/GPR signaling to generate asymmetry for spindle positioning in response to PAR and MES-1/SRC-1 signaling.
abstract: G-protein signaling plays important roles in asymmetric cell division. In C. elegans embryos, homologs of receptor-independent G protein activators, GPR-1 and GPR-2 (GPR-1/2), function together with Galpha (GOA-1 and GPA-16) to generate asymmetric spindle pole elongation during divisions in the P lineage. Although Galpha is uniformly localized at the cell cortex, the cortical localization of GPR-1/2 is asymmetric in dividing P cells. In this report, we show that the asymmetry of GPR-1/2 localization depends on PAR-3 and its downstream intermediate LET-99. Furthermore, in addition to its involvement in spindle elongation, Galpha is required for the intrinsically programmed nuclear rotation event that orients the spindle in the one-cell. LET-99 functions antagonistically to the Galpha/GPR-1/2 signaling pathway, providing an explanation for how Galpha-dependent force is regulated asymmetrically by PAR polarity cues during both nuclear rotation and anaphase spindle elongation. In addition, Galpha and LET-99 are required for spindle orientation during the extrinsically polarized division of EMS cells. In this cell, both GPR-1/2 and LET-99 are asymmetrically localized in response to the MES-1/SRC-1 signaling pathway. Their localization patterns at the EMS/P2 cell boundary are complementary, suggesting that LET-99 and Galpha/GPR-1/2 signaling function in opposite ways during this cell division as well. These results provide insight into how polarity cues are transmitted into specific spindle positions in both extrinsic and intrinsic pathways of asymmetric cell division.
authors.affiliation: Section of Molecular and Cellular Biology, University of California, Davis, CA 95616, USA.
authors.forename: Meng-Fu Bryan
authors.initials: MF
authors.lastname: Tsou
authors.forename: Adam
authors.initials: A
authors.lastname: Hayashi
authors.forename: Lesilee S
authors.initials: LS
authors.lastname: Rose
mesh_terms: D000818:Animals; D017173:Caenorhabditis elegans / Q000033:anatomy & histology / Q000196:embryology / Q000235:genetics / Q000378:metabolism; D029742:Caenorhabditis elegans Proteins / Q000235:genetics / Q000378:metabolism*; D002352:Carrier Proteins / Q000235:genetics / Q000378:metabolism*; D019070:Cell Lineage; D002467:Cell Nucleus / Q000378:metabolism; D016764:Cell Polarity; D009363:Neoplasm Proteins / Q000235:genetics / Q000378:metabolism*; D009687:Nuclear Proteins / Q000235:genetics / Q000378:metabolism*; D010641:Phenotype; D017346:Protein Serine-Threonine Kinases; D034622:RNA Interference; D011993:Recombinant Fusion Proteins / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction / Q000502:physiology*; D008941:Spindle Apparatus / Q000378:metabolism*; D000070584:Tripartite Motif Proteins
chemical_list: D029742:Caenorhabditis elegans Proteins; D002352:Carrier Proteins; D009363:Neoplasm Proteins; D009687:Nuclear Proteins; D017346:Protein Serine-Threonine Kinases; D011993:Recombinant Fusion Proteins; C475458:G protein regulator 1, C elegans; C475459:G protein regulator 2, C elegans; C467518:LET-99 protein, C elegans; C415743:Mes-1 protein, C elegans; C435227:TRIM47 protein, human; D000070584:Tripartite Motif Proteins; C097238:PAR-3 protein, C elegans