XAgonist-independent GPCR activity regulates anterior-posterior targeting of olfactory sensory neurons

Ai Nakashima, Haruki Takeuchi, Takeshi Imai, Harumi Saito, Hiroshi Kiyonari, Takaya Abe, Min Chen, Lee S. Weinstein, C. Ron Yu, Daniel R. Storm, Hirofumi Nishizumi, Hitoshi Sakano

研究成果: Contribution to journalArticle査読

85 被引用数 (Scopus)

抄録

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 β2-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.

本文言語英語
ページ(範囲)X1314-1325
ジャーナルCell
154
6
DOI
出版ステータス出版済み - 9 12 2013
外部発表はい

All Science Journal Classification (ASJC) codes

  • Biochemistry, Genetics and Molecular Biology(all)

フィンガープリント 「XAgonist-independent GPCR activity regulates anterior-posterior targeting of olfactory sensory neurons」の研究トピックを掘り下げます。これらがまとまってユニークなフィンガープリントを構成します。

引用スタイル