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

Joiner, Mei-ling A.; Lisé, Marie-France; Yuen, Eunice Y.; Kam, Angel Y.F.; Zhang, Mingxu; Hall, Duane D.; Malik, Zulfiqar Ali; Qian, Hai; Chen, Yucui; Ulrich, Jason D.; Burette, A; Weinberg, Richard J.; Law, Ping Yee; El-Husseini, Alaa; Yan, Zhen; Hell, Johannes

doi:10.1038/emboj.2009.344

Cited by 94 publications

(161 citation statements)

References 74 publications

Supporting

Mentioning

149

Contrasting

Order By: Relevance

“…Through such coupling, AKAP5 could bring PKA into close proximity with GPCRs and their effectors to regulate local cAMP signaling (17,18). ␤1AR and ␤2AR are the only GPCR that have, so far, been shown to form such a complex, which interacts with AKAP5 via SAP97 and PSD-95 (23,31). The ionotropic AMPA-type glutamate receptor subunit GluR1 also forms a PDZ motif-dependent complex with MAGUKs and AKAP5 (15,16).…”

Section: Discussionmentioning

confidence: 99%

G protein-coupled Receptor 30 (GPR30) Forms a Plasma Membrane Complex with Membrane-associated Guanylate Kinases (MAGUKs) and Protein Kinase A-anchoring Protein 5 (AKAP5) That Constitutively Inhibits cAMP Production

Broselid

Berg

Chavera

et al. 2014

Journal of Biological Chemistry

View full text Add to dashboard Cite

Background: GPR30 plays important roles in cardiometabolic regulation and cancer. Results: GPR30 forms a complex with a MAGUK and AKAP5 that constitutively inhibits cAMP production independently of G i/o and retains receptors in the plasma membrane. Conclusion:The GPR30-MAGUK-AKAP5 complex mediates receptor signaling. Significance: These results present a new mechanism by which a receptor inhibits cAMP production.

show abstract

Section: Discussionmentioning

confidence: 99%

G protein-coupled Receptor 30 (GPR30) Forms a Plasma Membrane Complex with Membrane-associated Guanylate Kinases (MAGUKs) and Protein Kinase A-anchoring Protein 5 (AKAP5) That Constitutively Inhibits cAMP Production

Broselid

Berg

Chavera

et al. 2014

Journal of Biological Chemistry

View full text Add to dashboard Cite

show abstract

“…The b 2 receptor activation can stimulate the PKA-dependent phosphorylation of the GluR1 subunit of AMPAR associated with the b 2 receptor and then increase membrane GluR1 expression at postsynaptic sites (Joiner et al, 2010). Several studies have suggested that extinction that induces AMPAR trafficking is distinct in different brain areas.…”

Section: Mechanism That Underlies the Role Of Hippocampal Ne In The Pmentioning

confidence: 99%

Delayed Noradrenergic Activation in the Dorsal Hippocampus Promotes the Long-Term Persistence of Extinguished Fear

Chai

Liu

Xue

et al. 2014

Neuropsychopharmacol

View full text Add to dashboard Cite

Fear extinction has been extensively studied, but little is known about the molecular processes that underlie the persistence of extinction long-term memory (LTM). We found that microinfusion of norepinephrine (NE) into the CA1 area of the dorsal hippocampus during the early phase (0 h) after extinction enhanced extinction LTM at 2 and 14 days after extinction. Intra-CA1 infusion of NE during the late phase (12 h) after extinction selectively promoted extinction LTM at 14 days after extinction that was blocked by the b-receptor antagonist propranolol, protein kinase A (PKA) inhibitor Rp-cAMPS, and protein synthesis inhibitors anisomycin and emetine. The phosphorylation levels of PKA, cyclic adenosine monophosphate response element-binding protein (CREB), GluR1, and the membrane GluR1 level were increased by NE during the late phase after extinction that was also blocked by propranolol and Rp-cAMPS. These results suggest that the enhancement of extinction LTM persistence induced by NE requires the activation of the b-receptor/PKA/CREB signaling pathway and membrane GluR1 trafficking. Moreover, extinction increased the phosphorylation levels of Erk1/2, CREB, and GluR1, and the membrane GluR1 level during the late phase, and anisomycin/emetine alone disrupted the persistence of extinction LTM, indicating that the persistence of extinction LTM requires late-phase protein synthesis in the CA1. Propranolol and Rp-cAMPS did not completely disrupt the persistence of extinction LTM, suggesting that another b-receptor/PKA-independent mechanism underlies the persistence of extinction LTM. Altogether, our results showed that enhancing hippocampal noradrenergic activity during the late phase after extinction selectively promotes the persistence of extinction LTM.

show abstract

“…Elegant studies by Hell and colleagues (26,27) have suggested that ACs are recruited into larger signaling networks that include ␤-adrenergic receptors, kinases, and ion channels. We have shown that AKAP79 functions to scaffold its cargo of signaling enzymes to synaptic AMPA receptors (9).…”

Section: Ampa Receptor-associated Ac Activity Is Mediated In Part By mentioning

confidence: 99%

AKAP79 Interacts with Multiple Adenylyl Cyclase (AC) Isoforms and Scaffolds AC5 and -6 to α-Amino-3-hydroxyl-5-methyl-4-isoxazole-propionate (AMPA) Receptors

Efendiev

Samelson

Nguyen

et al. 2010

Journal of Biological Chemistry

100

129

View full text Add to dashboard Cite

Spatiotemporal specificity of cAMP action is best explained by targeting protein kinase A (PKA) to its substrates by A-kinase-anchoring proteins (AKAPs). At synapses in the brain, AKAP79/150 incorporates PKA and other regulatory enzymes into signal transduction networks that include ␤-adrenergic receptors, ␣-amino-3-hydroxyl-5-methyl-4-isoxazole-propionate (AMPA), and N-methyl-D-aspartic acid receptors. We previously showed that AKAP79/150 clusters PKA with type 5 adenylyl cyclase (AC5) to assemble a negative feedback loop in which the anchored kinase phosphorylates AC5 to dynamically suppress cAMP synthesis. We now show that AKAP79 can associate with multiple AC isoforms. The N-terminal regions of AC5, -6, and -9 mediate this protein-protein interaction. Localized activation of PKA 2 triggers a plethora of intracellular signaling processes (1). Precise control of these phosphorylation events is often achieved by restricted activation of PKA in discrete microenvironments. AKAPs participate in this process by tethering the kinase close to preferred substrates. AKAPs now represent a family of 43 diverse but functionally related proteins that bind the regulatory subunit dimer of the PKA holoenzyme (2).AKAPs have been identified in a range of species, tissues, and cellular compartments. The AKAP79/150 group of anchoring proteins is perhaps the best understood member of this class of signal-organizing proteins. AKAP79/150 consists of three orthologs: bovine AKAP75, human AKAP79, and murine AKAP150. Although originally identified in the postsynaptic densities of neurons, this group of anchoring proteins is also expressed in a variety of other tissues. In addition to binding PKA, AKAP79 has the ability to bind protein phosphatase 2B (3) and protein kinase C (PKC) (4, 5). By organizing these signal transduction and signal termination enzymes in the same location, AKAP79 provides a platform to facilitate the bidirectional control of cAMP-and calcium-mediated signaling events.Although anchoring of PKA with its substrates provides an efficient mechanism for the spatial regulation necessary for selectivity of cAMP signaling, it was not clear how local pools of cAMP are managed. We have shown that AC isoforms can specifically interact with three different AKAP complexes, AKAP79, Yotiao, and mAKAP, to regulate events downstream of cAMP production (6 -8). We have also demonstrated that anchoring of AC5 to an AKAP79/150 complex provides negative feedback on AC5 via PKA phosphorylation of AC5 within the complex (6).Although characterization of the AKAP79-AC5 interaction has shed some light on the advantages gained by localizing different components of cAMP signaling pathways, several key issues remain unresolved. First of all, do other AC isoforms interact with AKAP79 or other anchoring proteins? Secondly, are AC isoforms recruited into larger signaling networks via their protein-protein interactions with AKAP79? AKAP79/150 has been shown to form a multiprotein signaling complex with AMPA and NMDA receptors (9 -11), adhesion mol...

show abstract

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

Cited by 94 publications

References 74 publications

G protein-coupled Receptor 30 (GPR30) Forms a Plasma Membrane Complex with Membrane-associated Guanylate Kinases (MAGUKs) and Protein Kinase A-anchoring Protein 5 (AKAP5) That Constitutively Inhibits cAMP Production

G protein-coupled Receptor 30 (GPR30) Forms a Plasma Membrane Complex with Membrane-associated Guanylate Kinases (MAGUKs) and Protein Kinase A-anchoring Protein 5 (AKAP5) That Constitutively Inhibits cAMP Production

Delayed Noradrenergic Activation in the Dorsal Hippocampus Promotes the Long-Term Persistence of Extinguished Fear

AKAP79 Interacts with Multiple Adenylyl Cyclase (AC) Isoforms and Scaffolds AC5 and -6 to α-Amino-3-hydroxyl-5-methyl-4-isoxazole-propionate (AMPA) Receptors

Contact Info

Product

Resources

About