期刊
CELL
卷 154, 期 6, 页码 1314-1325出版社
CELL PRESS
DOI: 10.1016/j.cell.2013.08.033
关键词
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资金
- PRESTO program of Japan Science and Technology Corporation
- Toray Science Foundation
- Sumitomo Foundation
- Nakajima Foundation
- Mitsubishi Foundation
- Japan Foundation for Applied Enzymology
- Ministry of Education, Culture, Sports, Science and Technology (MEXT) of Japan
- MEXT of Japan
- Grants-in-Aid for Scientific Research [23680038, 24000014, 23300140] Funding Source: KAKEN
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 beta 2-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 G(s), but not G(olf), 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.
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