Assembly of a β2-adrenergic receptor—GluR1 signalling complex for localized cAMP signalling
Open Access
- 26 November 2009
- journal article
- Published by Springer Science and Business Media LLC in The EMBO Journal
- Vol. 29 (2), 482-495
- https://doi.org/10.1038/emboj.2009.344
Abstract
Central noradrenergic signalling mediates arousal and facilitates learning through unknown molecular mechanisms. Here, we show that the β2‐adrenergic receptor (β2AR), the trimeric Gs protein, adenylyl cyclase, and PKA form a signalling complex with the AMPA‐type glutamate receptor subunit GluR1, which is linked to the β2AR through stargazin and PSD‐95 and their homologues. Only GluR1 associated with the β2AR is phosphorylated by PKA on β2AR stimulation. Peptides that interfere with the β2AR–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 β2AR–cAMP cascade into a supramolecular signalling complex and thus allows highly localized and selective regulation of one of its major target proteins.Keywords
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