| First Author | Nakashima A | Year | 2013 |
| Journal | Cell | Volume | 154 |
| Issue | 6 | Pages | 1314-25 |
| PubMed ID | 24034253 | Mgi Jnum | J:204616 |
| Mgi Id | MGI:5532888 | Doi | 10.1016/j.cell.2013.08.033 |
| Citation | Nakashima A, et al. (2013) Agonist-independent GPCR activity regulates anterior-posterior targeting of olfactory sensory neurons. Cell 154(6):1314-25 |
| abstractText | G-protein-coupled receptors (GPCRs) are known to possess two different conformations, active and inactive, and they spontaneously alternate between the two in the absence of ligands. Here, we analyzed the agonist-independent GPCR activity for its possible role in receptor-instructed axonal projection. We generated transgenic mice expressing activity mutants of the beta2-adrenergic receptor, a well-characterized GPCR with the highest homology to odorant receptors (ORs). We found that mutants with altered agonist-independent activity changed the transcription levels of axon-targeting molecules--e.g., Neuropilin-1 and Plexin-A1--but not of glomerular segregation molecules--e.g., Kirrel2 and Kirrel3--thus causing shifts in glomerular locations along the anterior-posterior (A-P) axis. Knockout and in vitro experiments demonstrated that Gs, but not Golf, is responsible for mediating the agonist-independent GPCR activity. We conclude that the equilibrium of conformational transitions set by each OR is the major determinant of expression levels of A-P-targeting molecules. |
