Oriented Cell Division in the C. elegans Embryo Is Coordinated by G-Protein Signaling Dependent on the Adhesion GPCR LAT-1

• Published in: PLoS genetics Vol. 11; no. 10; p. e1005624
• Main Authors: Müller, Antje, Winkler, Jana, Fiedler, Franziska, Sastradihardja, Tania, Binder, Claudia, Schnabel, Ralf, Kungel, Jana, Rothemund, Sven, Hennig, Christian, Schöneberg, Torsten, Prömel, Simone
• Format: Journal Article
• Language: English
• Published: United States Public Library of Science 01.10.2015; Public Library of Science (PLoS)
• Subjects: Adenylyl Cyclases - genetics; Adenylyl Cyclases - metabolism; Analysis; Animals; Caenorhabditis elegans - genetics; Caenorhabditis elegans - growth & development; Cell Adhesion - genetics; Cell division; Cell Division - genetics; Cyclic AMP - genetics; Embryo; Embryo, Nonmammalian; Embryos; Experiments; G proteins; GTP-Binding Proteins - genetics; GTP-Binding Proteins - metabolism; Large Neutral Amino Acid-Transporter 1 - genetics; Large Neutral Amino Acid-Transporter 1 - metabolism; Nematodes; Peptides; Proteins; Signal Transduction
• ISSN: 1553-7404; 1553-7390; 1553-7404
• DOI: 10.1371/journal.pgen.1005624

Orientation of spindles and cell division planes during development of many species ensures that correct cell-cell contacts are established, which is vital for proper tissue formation. This is a tightly regulated process involving a complex interplay of various signals. The molecular mechanisms underlying several of these pathways are still incompletely understood. Here, we identify the signaling cascade of the C. elegans latrophilin homolog LAT-1, an essential player in the coordination of anterior-posterior spindle orientation during the fourth round of embryonic cell division. We show that the receptor mediates a G protein-signaling pathway revealing that G-protein signaling in oriented cell division is not solely GPCR-independent. Genetic analyses showed that through the interaction with a Gs protein LAT-1 elevates intracellular cyclic AMP (cAMP) levels in the C. elegans embryo. Stimulation of this G-protein cascade in lat-1 null mutant nematodes is sufficient to orient spindles and cell division planes in the embryo in the correct direction. Finally, we demonstrate that LAT-1 is activated by an intramolecular agonist to trigger this cascade. Our data support a model in which a novel, GPCR-dependent G protein-signaling cascade mediated by LAT-1 controls alignment of cell division planes in an anterior-posterior direction via a metabotropic Gs-protein/adenylyl cyclase pathway by regulating intracellular cAMP levels.