| First Author | Bonanomi D | Year | 2012 |
| Journal | Cell | Volume | 148 |
| Issue | 3 | Pages | 568-82 |
| PubMed ID | 22304922 | Mgi Jnum | J:180801 |
| Mgi Id | MGI:5307244 | Doi | 10.1016/j.cell.2012.01.024 |
| Citation | Bonanomi D, et al. (2012) Ret Is a Multifunctional Coreceptor that Integrates Diffusible- and Contact-Axon Guidance Signals. Cell 148(3):568-82 |
| abstractText | Growing axons encounter multiple guidance cues, but it is unclear how separate signals are resolved and integrated into coherent instructions for growth cone navigation. We report that glycosylphosphatidylinositol (GPI)-anchored ephrin-As function as "reverse" signaling receptors for motor axons when contacted by transmembrane EphAs present in the dorsal limb. Ephrin-A receptors are thought to depend on transmembrane coreceptors for transmitting signals intracellularly. We show that the receptor tyrosine kinase Ret is required for motor axon attraction mediated by ephrin-A reverse signaling. Ret also mediates GPI-anchored GFRalpha1 signaling in response to GDNF, a diffusible chemoattractant in the limb, indicating that Ret is a multifunctional coreceptor for guidance molecules. Axons respond synergistically to coactivation by GDNF and EphA ligands, and these cooperative interactions are gated by GFRalpha1 levels. Our studies uncover a hierarchical GPI-receptor signaling network that is constructed from combinatorial components and integrated through Ret using ligand coincidence detection. |
