| RRC ID |
53499
|
| 著者 |
Müller A, Winkler J, Fiedler F, Sastradihardja T, Binder C, Schnabel R, Kungel J, Rothemund S, Hennig C, Schöneberg T, Prömel S.
|
| タイトル |
Oriented Cell Division in the C. elegans Embryo Is Coordinated by G-Protein Signaling Dependent on the Adhesion GPCR LAT-1.
|
| ジャーナル |
PLoS Genet
|
| Abstract |
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.
|
| 巻・号 |
11(10)
|
| ページ |
e1005624
|
| 公開日 |
2015-10-1
|
| DOI |
10.1371/journal.pgen.1005624
|
| PII |
PGENETICS-D-15-01575
|
| PMID |
26505631
|
| PMC |
PMC4624771
|
| MeSH |
Adenylyl Cyclases / genetics
Adenylyl Cyclases / metabolism
Animals
Caenorhabditis elegans / genetics*
Caenorhabditis elegans / growth & development
Cell Adhesion / genetics
Cell Division / genetics*
Cyclic AMP / genetics
Embryo, Nonmammalian
GTP-Binding Proteins / genetics
GTP-Binding Proteins / metabolism*
Large Neutral Amino Acid-Transporter 1 / genetics*
Large Neutral Amino Acid-Transporter 1 / metabolism
Signal Transduction
|
| IF |
5.224
|
| 引用数 |
36
|
| リソース情報 |
| 線虫 |
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