Assembly of a beta2-adrenergic receptor--GluR1 signalling complex for localized cAMP signalling.
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.
Joiner
Mei-ling A
ML
Department of Pharmacology, University of Iowa, Iowa City, IA, USA.
Lisé
Marie-France
MF
Yuen
Eunice Y
EY
Kam
Angel Y F
AY
Zhang
Mingxu
M
Hall
Duane D
DD
Malik
Zulfiqar A
ZA
Qian
Hai
H
Chen
Yucui
Y
Ulrich
Jason D
JD
Burette
Alain C
AC
Weinberg
Richard J
RJ
Law
Ping-Yee
PY
El-Husseini
Alaa
A
Yan
Zhen
Z
Hell
Johannes W
JW
D000262:Adenylyl Cyclases / Q000032:analysis / Q000378:metabolism*; D000818:Animals; D015220:Calcium Channels / Q000378:metabolism; D002478:Cells, Cultured; D002540:Cerebral Cortex / Q000378:metabolism; D017868:Cyclic AMP-Dependent Protein Kinases / Q000032:analysis / Q000378:metabolism*; D000076122:Disks Large Homolog 4 Protein; D004594:Electrophysiology; D019205:GTP-Binding Protein alpha Subunits, Gs / Q000032:analysis / Q000378:metabolism; D005786:Gene Expression Regulation; D006624:Hippocampus / Q000166:cytology; D047908:Intracellular Signaling Peptides and Proteins / Q000378:metabolism; D008565:Membrane Proteins / Q000378:metabolism; D009474:Neurons / Q000166:cytology; D051381:Rats; D017207:Rats, Sprague-Dawley; D018091:Receptors, AMPA / Q000032:analysis* / Q000235:genetics / Q000378:metabolism*; D018343:Receptors, Adrenergic, beta-2 / Q000032:analysis / Q000378:metabolism*
D000262:Adenylyl Cyclases; D015220:Calcium Channels; D017868:Cyclic AMP-Dependent Protein Kinases; D000076122:Disks Large Homolog 4 Protein; D019205:GTP-Binding Protein alpha Subunits, Gs; D047908:Intracellular Signaling Peptides and Proteins; D008565:Membrane Proteins; D018091:Receptors, AMPA; D018343:Receptors, Adrenergic, beta-2; C491911:Cacng2 protein, rat; C501449:Dlg4 protein, rat