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: ジャーナルへの寄稿記事

61 引用 (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.

元の言語英語
ジャーナルCell
154
発行部数6
DOI
出版物ステータス出版済み - 9 12 2013

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Olfactory Receptor Neurons
G-Protein-Coupled Receptors
Neurons
Odorant Receptors
Molecules
Neuropilin-1
Golf
Transcription
Adrenergic Receptors
Transgenic Mice
Axons
Conformations
Ligands
Experiments

All Science Journal Classification (ASJC) codes

  • Biochemistry, Genetics and Molecular Biology(all)

これを引用

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

:: Cell, 巻 154, 番号 6, 12.09.2013.

研究成果: ジャーナルへの寄稿記事

Nakashima, A, Takeuchi, H, Imai, T, Saito, H, Kiyonari, H, Abe, T, Chen, M, Weinstein, LS, Yu, CR, Storm, DR, Nishizumi, H & Sakano, H 2013, 'XAgonist-independent GPCR activity regulates anterior-posterior targeting of olfactory sensory neurons', Cell, 巻. 154, 番号 6. https://doi.org/10.1016/j.cell.2013.08.033
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. / XAgonist-independent GPCR activity regulates anterior-posterior targeting of olfactory sensory neurons. :: Cell. 2013 ; 巻 154, 番号 6.
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AU - Kiyonari, Hiroshi

AU - Abe, Takaya

AU - Chen, Min

AU - Weinstein, Lee S.

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AU - Sakano, Hitoshi

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