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A High-content Imaging Workflow to Study Grb2 Signaling Complexes by Expression Cloning
Published on: October 30, 2012
Assembly of a beta2-adrenergic receptor--GluR1 signalling complex for localized cAMP signalling
Mei-ling A Joiner1, Marie-France Lisé, Eunice Y Yuen
1Department of Pharmacology, University of Iowa, Iowa City, IA, USA.
None:
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(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 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.
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