Selective interactions of spinophilin with the C-terminal domains of the δ- and μ-opioid receptors and G proteins differentially modulate opioid receptor signaling

Fourla, Danai-Dionysia; Παπακωνσταντίνου, Μαρία-Παγώνα; Vrana, Stavroula-Maria; Georgoussi, Zafiroula

doi:10.1016/j.cellsig.2012.08.002

Cited by 21 publications

(30 citation statements)

References 37 publications

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“…Thus, by arresting G protein activity, RGS proteins are key regulators of opioid receptor signaling (Xie and Palmer, 2005;Traynor, 2012). As mentioned in section IX.C.2.b, RGS4 directly interacts with DOPr to negatively modulate receptor signaling via cAMP and ERK pathways both in heterologous (Leontiadis et al, 2009) and endogenous ) expression systems, an effect that is potentiated by spinophilin (Fourla et al, 2012). Since RGS4 and Ga subunits bind the receptor at common residues (Georgoussi et al, 2006), it is not yet clear whether RGS4 inhibition of DOPr signaling is due to normal acceleration of GTPase activity or to its competition with the G protein for binding to the receptor.…”

Section: E D-opioid Receptor Regulation By Regulators Of G Protein Smentioning

confidence: 99%

“…The same juxtamembrane region of the DOPr C-terminal domain that interacts with RGS4 and Ga subunits as well as the third ICL also binds spinophilin, a multidomain scaffold protein that is highly enriched in dendritic spines (Fourla et al, 2012). By simultaneously binding RGS4, the receptor, Ga and Gbg subunits spinophilin would stabilize a multimeric signaling complex that enhances RGS4 modulation of DOPr signaling (Fourla et al, 2012). The next category of DOPr-interacting proteins corresponds to those involved in receptor desensitization and trafficking.…”

Section: D-opioid Receptor Pharmacologymentioning

confidence: 99%

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Molecular Pharmacology ofδ-Opioid Receptors

et al. 2016

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Section: E D-opioid Receptor Regulation By Regulators Of G Protein Smentioning

confidence: 99%

Section: D-opioid Receptor Pharmacologymentioning

confidence: 99%

Molecular Pharmacology ofδ-Opioid Receptors

et al. 2016

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“…Similarly, spinophilin recruits RGS4 to m3AChR, and like RGS8, RGS4 antagonizes m3AChR inositol phosphate signaling (Ruiz de Azua et al, 2012). Spinophilin also promotes m-opioid receptor (mOR)-mediated signaling via Ga i , but inhibits mOR-mediated ERK activation, while facilitating mOR endocytosis (Charlton et al, 2008;Fourla et al, 2012).…”

Section: Additional Gpcr-interacting Pdz Proteinsmentioning

confidence: 99%

“…The interaction between spinophilin and opioid receptors appears to occur via the opioid receptor third intracellular loop and a conserved region of the carboxyl-termini, which is proximal to the seventh transmembrane domain (Fourla et al, 2012). Interestingly, this region appears to correlate with a small helical region identified in many class A rhodopsin-like GPCRs as helix 8 (Huynh et al, 2009).…”

Section: Additional Gpcr-interacting Pdz Proteinsmentioning

confidence: 99%

PDZ Protein Regulation of G Protein–Coupled Receptor Trafficking and Signaling Pathways

Dunn

Ferguson

2015

Mol Pharmacol

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G protein-coupled receptors (GPCRs) contribute to the regulation of every aspect of human physiology and are therapeutic targets for the treatment of numerous diseases. As a consequence, understanding the myriad of mechanisms controlling GPCR signaling and trafficking is essential for the development of new pharmacological strategies for the treatment of human pathologies. Of the many GPCR-interacting proteins, postsynaptic density protein of 95 kilodaltons, disc large, zona occludens-1 (PDZ) domain-containing proteins appear most abundant and have similarly been implicated in disease mechanisms. PDZ proteins play an important role in regulating receptor and channel protein localization within synapses and tight junctions and function to scaffold intracellular signaling protein complexes. In the current study, we review the known functional interactions between PDZ domain-containing proteins and GPCRs and provide insight into the potential mechanisms of action. These PDZ domain-containing proteins include the membraneassociated guanylate-like kinases [postsynaptic density protein of 95 kilodaltons; synapse-associated protein of 97 kilodaltons; postsynaptic density protein of 93 kilodaltons; synapse-associated protein of 102 kilodaltons; discs, large homolog 5; caspase activation and recruitment domain and membrane-associated guanylate-like kinase domain-containing protein 3; membrane protein, palmitoylated 3; calcium/calmodulin-dependent serine protein kinase; membrane-associated guanylate kinase protein (MAGI)-1, MAGI-2, and MAGI-3], Na 1 /H 1 exchanger regulatory factor proteins (NHERFs) (NHERF1, NHERF2, PDZ domaincontaining kidney protein 1, and PDZ domain-containing kidney protein 2), Golgi-associated PDZ proteins (Ga-binding protein interacting protein, C-terminus and CFTR-associated ligand), PDZ domain-containing guanine nucleotide exchange factors (GEFs) 1 and 2, regulator of G protein signaling (RGS)-homology-RhoGEFs (PDZ domain-containing RhoGEF and leukemia-associated RhoGEF), RGS3 and RGS12, spinophilin and neurabin-1, SRC homology 3 domain and multiple ankyrin repeat domain (Shank) proteins (Shank1, Shank2, and Shank3), partitioning defective proteins 3 and 6, multiple PDZ protein 1, Tamalin, neuronal nitric oxide synthase, syntrophins, protein interacting with protein kinase C a 1, syntenin-1, and sorting nexin 27.

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“…Moreover, Spn binds to the 3i loop of CCKA and CCKB receptors (Wang et al, 2007). The receptor binding domain of Spn also associates with the 3i loop and a conserved region of the C-terminal tails of δ-and µ-OR (Fourla et al, 2012). Spn also interacts with the ionotropic NMDA and AMPA-type glutamate receptors.…”

Section: -The Spinophilin Interactomementioning

confidence: 99%

The tumour suppressor function of the scaffolding protein spinophilin

Sarrouilhe¹,

Ladevèze²

2014

Atlas of Genetics and Cytogenetics in Oncology and Haematology

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Spinophilin is a scaffolding protein with modular domains that govern its interaction with a large number of cellular proteins. The Spinophilin gene locus is localized at chromosome 17q21, a chromosomal region frequently affected by genomic instability in different human tumours. The scaffolding protein interacts with the tumour-suppressor ARF which has suggested a role for Spinophilin in cell growth. More recently, in vitro and in vivo studies demonstrated that Spinophilin is a new tumour suppressor acting via the regulation of pRb. A clear downregulation of Spinophilin is found in several human cancer types. Moreover, Spinophilin loss is associated with a poor patient prognosis in carcinoma. Currently, there are controversial findings regarding a functional relationship between Spinophilin and p53 in cell cycle regulation and in carcinogenesis. Here we present the available data regarding Spinophilin function as a tumour suppressor.

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Selective interactions of spinophilin with the C-terminal domains of the δ- and μ-opioid receptors and G proteins differentially modulate opioid receptor signaling

Cited by 21 publications

References 37 publications

Molecular Pharmacology ofδ-Opioid Receptors

Molecular Pharmacology ofδ-Opioid Receptors

PDZ Protein Regulation of G Protein–Coupled Receptor Trafficking and Signaling Pathways

The tumour suppressor function of the scaffolding protein spinophilin

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