Premium
Assembly of a β 2 ‐adrenergic receptor—GluR1 signalling complex for localized cAMP signalling
Author(s) -
Joiner Meiling A,
Lisé MarieFrance,
Yuen Eunice Y,
Kam Angel Y F,
Zhang Mingxu,
Hall Duane D,
Malik Zulfiqar A,
Qian Hai,
Chen Yucui,
Ulrich Jason D,
Burette Alain C,
Weinberg Richard J,
Law PingYee,
ElHusseini Alaa,
Yan Zhen,
Hell Johannes W
Publication year - 2010
Publication title -
the embo journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 7.484
H-Index - 392
eISSN - 1460-2075
pISSN - 0261-4189
DOI - 10.1038/emboj.2009.344
Subject(s) - library science , computer science
Central noradrenergic signalling mediates arousal and facilitates learning through unknown molecular mechanisms. Here, we show that the β 2 ‐adrenergic receptor (β 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 β 2 AR through stargazin and PSD‐95 and their homologues. Only GluR1 associated with the β 2 AR is phosphorylated by PKA on β 2 AR stimulation. Peptides that interfere with the β 2 AR–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 β 2 AR–cAMP cascade into a supramolecular signalling complex and thus allows highly localized and selective regulation of one of its major target proteins.