Agonist-Independent GPCR Activity Regulates Anterior-Posterior Targeting of Olfactory Sensory Neurons

作者：Nakashima Ai; Takeuchi Haruki; Imai Takeshi; Saito Harumi; Kiyonari Hiroshi; Abe Takaya; Chen Min; Weinstein Lee S; Yu C Ron; Storm Daniel R; Nishizumi Hirofumi; Sakano Hitoshi^*

来源：Cell, 2013, 154(6): 1314-1325.

DOI：10.1016/j.cell.2013.08.033

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.

• 出版日期2013-9-12
• 单位河北医科大学