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

Research output: Contribution to journalArticle

70 Citations (Scopus)

Abstract

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.

Original languageEnglish
Pages (from-to)X1314-1325
JournalCell
Volume154
Issue number6
DOIs
Publication statusPublished - Sep 12 2013
Externally publishedYes

All Science Journal Classification (ASJC) codes

  • Biochemistry, Genetics and Molecular Biology(all)

Fingerprint Dive into the research topics of 'XAgonist-independent GPCR activity regulates anterior-posterior targeting of olfactory sensory neurons'. Together they form a unique fingerprint.

  • Cite this

    Nakashima, A., Takeuchi, H., Imai, T., Saito, H., Kiyonari, H., Abe, T., Chen, M., Weinstein, L. S., Yu, C. R., Storm, D. R., Nishizumi, H., & Sakano, H. (2013). XAgonist-independent GPCR activity regulates anterior-posterior targeting of olfactory sensory neurons. Cell, 154(6), X1314-1325. https://doi.org/10.1016/j.cell.2013.08.033