Assembly of a β2-adrenergic receptor-GluR1 signalling complex for localized cAMP signalling

被引：84

作者：

Joiner, Mei-ling A. ^{[1
]}

Lise, Marie-France ^{[2
,3
]}

Yuen, Eunice Y. ^{[4
]}

Kam, Angel Y. F. ^{[5
]}

Zhang, Mingxu ^{[1
]}

Hall, Duane D. ^{[1
]}

Malik, Zulfiqar A. ^{[1
]}

Qian, Hai ^{[1
]}

Chen, Yucui ^{[1
]}

Ulrich, Jason D. ^{[1
]}

Burette, Alain C. ^{[6
,7
]}

Weinberg, Richard J. ^{[6
,7
]}

Law, Ping-Yee ^{[5
]}

El-Husseini, Alaa ^{[2
,3
]}

Yan, Zhen ^{[4
]}

Hell, Johannes W. ^{[1
]}

机构：

[1] Univ Iowa, Dept Pharmacol, Iowa City, IA 52242 USA

[2] Univ British Columbia, Dept Psychiat, Vancouver, BC, Canada

[3] Univ British Columbia, Brain Res Ctr, Vancouver, BC V5Z 1M9, Canada

[4] SUNY Buffalo, Dept Physiol, Buffalo, NY 14260 USA

[5] Univ Minnesota, Dept Pharmacol, Minneapolis, MN 55455 USA

[6] Univ N Carolina, Dept Cell & Dev Biol, Chapel Hill, NC USA

[7] Univ N Carolina, Ctr Neurosci, Chapel Hill, NC USA

来源：

EMBO JOURNAL | 2010年 / 29卷 / 02期

关键词：

adrenergic; AMPA; localized; signalling; DEPENDENT PROTEIN-KINASE; LONG-TERM POTENTIATION; BETA-ADRENERGIC MODULATION; HIPPOCAMPAL CA1 REGION; CA2+ CHANNEL CA(V)1.2; D-ASPARTATE RECEPTORS; AMPA RECEPTORS; DIFFERENTIAL REGULATION; FREQUENCY STIMULATION; GLUTAMATE RECEPTORS;

D O I：

10.1038/emboj.2009.344

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

Central noradrenergic signalling mediates arousal and facilitates learning through unknown molecular mechanisms. Here, we show that the beta(2)-adrenergic receptor (beta(2)AR), the trimeric G(s) protein, adenylyl cyclase, and PKA form a signalling complex with the AMPA-type glutamate receptor subunit GluR1, which is linked to the beta(2)AR through stargazin and PSD-95 and their homologues. Only GluR1 associated with the beta(2)AR is phosphorylated by PKA on beta(2)AR stimulation. Peptides that interfere with the beta 2AR-GluR1 association prevent this phosphorylation of GluR1. This phosphorylation increases GluR1 surface expression at postsynaptic sites and amplitudes of EPSCs and mEPSCs in prefrontal cortex slices. Assembly of all proteins involved in the classic beta(2)AR-cAMP cascade into a supramolecular signalling complex and thus allows highly localized and selective regulation of one of its major target proteins. The EMBO Journal (2010) 29, 482-495. doi: 10.1038/emboj.2009.344; Published online 26 November 2009

引用

页码：482 / 495

页数：14

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