μ-opioid and 5-HT1A receptors heterodimerize and show signalling crosstalk via G protein and MAP-kinase pathways

Cussac, Didier; Rauly‐Lestienne, Isabelle; Heusler, Peter; Finana, Frédéric; Cathala, Claudie; Bernois, Sophie; Vries, Luc De

doi:10.1016/j.cellsig.2012.04.010

Cited by 34 publications

(32 citation statements)

References 36 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Examination of the signalling properties showed that the μ receptor agonist could activate a Gα o protein that was covalently fused to 5‐HT 1A receptors only in cells coexpressing both receptors (Cussac et al ., ). In addition, phosphorylation of ERK1/2 induced following activation of μ receptors was blocked in the presence of the 5‐HT 1A receptor agonist (Cussac et al ., ). Examination of the trafficking properties of this heteromer shows that treatment with the agonist to one protomer did not induce internalization of the partner protomer (Cussac et al ., ).…”

Section: Other Heteromers Involving Opioid Receptorsmentioning

confidence: 99%

Revolution in GPCR signalling: opioid receptor heteromers as novel therapeutic targets: IUPHAR Review 10

Fujita

Gomes

Devi

2014

British J Pharmacology

View full text Add to dashboard Cite

GPCRs can interact with each other to form homomers or heteromers. Homomers involve interactions with the same receptor type while heteromers involve interactions between two different GPCRs. These receptor–receptor interactions modulate not only the binding but also the signalling and trafficking properties of individual receptors. Opioid receptor heteromerization has been extensively investigated with the objective of identifying novel therapeutic targets that are as potent as morphine but without the side effects associated with chronic morphine use. In this context, studies have described heteromerization between the different types of opioid receptors and between opioid receptors and a wide range of GPCRs including adrenoceptors, cannabinoid, 5‐HT, metabotropic glutamate and sensory neuron‐specific receptors. Recent advances in the field involving the generation of heteromer‐specific reagents (antibodies or ligands) or of membrane‐permeable peptides that disrupt the heteromer interaction are helping to elucidate the physiological role of opioid receptor heteromers and the contribution of the partner receptor to the side effects associated with opioid use. For example, studies using membrane‐permeable peptides targeting the heteromer interface have implicated μ and δ receptor heteromers in the development of tolerance to morphine, and heteromers of μ and gastrin‐releasing peptide receptors in morphine‐induced itch. In addition, a number of ligands that selectively target opioid receptor heteromers exhibit potent antinociception with a decrease in the side effects commonly associated with morphine use. In this review, we summarize the latest findings regarding the biological and functional characteristics of opioid receptor heteromers both in vitro and in vivo.

show abstract

Section: Other Heteromers Involving Opioid Receptorsmentioning

confidence: 99%

Revolution in GPCR signalling: opioid receptor heteromers as novel therapeutic targets: IUPHAR Review 10

Fujita

Gomes

Devi

2014

British J Pharmacology

View full text Add to dashboard Cite

show abstract

“…For 5-HT receptors, heterodimers of 5-HT 1A receptors have been reported with FGFR1 (Borroto-Escuela et al 2012), μ opioid (Cussac et al 2012), adenosineA2a (Lukasiewicz et al 2007), and galanin receptors (Fuxe et al 2012). 5-HT 2A receptor heterodimers have been reported with mGluR2 (Gonzalez-Maeso et al 2008; Rives et al, 2009; Moreno et al 2011) and D2 dopamine receptors (Albizu et al 2011; Lukasiewicz et al 2011), and 5-HT 4 -B2-AR heterodimers have been reported (Berthouze et al 2005).…”

Section: Introductionmentioning

confidence: 99%

Functional significance of serotonin receptor dimerization

Herrick‐Davis

2013

Exp Brain Res

View full text Add to dashboard Cite

The original model of G protein activation by a single G-protein-coupled receptor (GPCR) is giving way to a new model wherein two protomers of a GPCR dimer interact with a single G protein. This article will review the evidence suggesting that 5-HT receptors form dimers/oligomers and will compare the findings with results obtained from studies with other biogenic amine receptors. Topics to be covered include the origin or biogenesis of dimer formation, potential dimer interface(s), and oligomer size (dimer versus tetramer or higher order). The functional significance will be discussed in terms of G-protein activation following ligand binding to one or two protomers in a dimeric structure, the formation of heterodimers and the development of bivalent ligands.

show abstract

“…For instance, stimulation of cells expressing either 5-HT 1A R or mu-opioid receptors with specific agonists triggers in both cases, the activation of MAPK, cascade which desensitizes after 30 min of stimulation. Nonetheless, when both receptors are co-expressed, the activation of one receptor in the 5-HT 1A R/μ-opioid heterodimer inhibits MAPK activation of the other receptor (Cussac et al, 2012). On the other hand, biochemical studies accomplished in neuroblastoma N1E-115 cells revealed that 5-HT 1A R forms dimers and homo-oligomers, being dimers the prevalent species at the plasma membrane (Kobe et al, 2008; Woehler et al, 2009).…”

Section: -Ht1ar Forms Complex With Gpcrs: a Mechanism To Modulate Itmentioning

confidence: 99%

What Do We Really Know About 5-HT1A Receptor Signaling in Neuronal Cells?

Rojas

Fiedler

2016

Front. Cell. Neurosci.

View full text Add to dashboard Cite

Serotonin (5-HT) is a neurotransmitter that plays an important role in neuronal plasticity. Variations in the levels of 5-HT at the synaptic cleft, expression or dysfunction of 5-HT receptors may alter brain development and predispose to various mental diseases. Here, we review the transduction pathways described in various cell types transfected with recombinant 5-HT1A receptor (5-HT1AR), specially contrasting with those findings obtained in neuronal cells. The 5-HT1AR is detected in early stages of neural development and is located in the soma, dendrites and spines of hippocampal neurons. The 5-HT1AR differs from other 5-HT receptors because it is coupled to different pathways, depending on the targeted cell. The signaling pathway associated with this receptor is determined by Gα isoforms and some cascades involve βγ signaling. The activity of 5-HT1AR usually promotes a reduction in neuronal excitability and firing, provokes a variation in cAMP and Ca2+, levels which may be linked to specific types of behavior and cognition. Furthermore, evidence indicates that 5-HT1AR induces neuritogesis and synapse formation, probably by modulation of the neuronal cytoskeleton through MAPK and phosphoinositide-3-kinase (PI3K)-Akt signaling pathways. Advances in understanding the actions of 5-HT1AR and its association with different signaling pathways in the central nervous system will reveal their pivotal role in health and disease.

show abstract

μ-opioid and 5-HT1A receptors heterodimerize and show signalling crosstalk via G protein and MAP-kinase pathways

Cited by 34 publications

References 36 publications

Revolution in GPCR signalling: opioid receptor heteromers as novel therapeutic targets: IUPHAR Review 10

Revolution in GPCR signalling: opioid receptor heteromers as novel therapeutic targets: IUPHAR Review 10

Functional significance of serotonin receptor dimerization

What Do We Really Know About 5-HT1A Receptor Signaling in Neuronal Cells?

Contact Info

Product

Resources

About