PSD-95 regulates D1 dopamine receptor resensitization, but not receptor-mediated Gs-protein activation

Sun, Peihua; Wang, Jingru; Gu, Wei-hua; Cheng, Wei; Jin, Guo; Friedman, Eitan; Zheng, Jie; Zhen, Xuechu

doi:10.1038/cr.2009.30

Cited by 25 publications

(39 citation statements)

References 37 publications

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“…Indeed, PSD-95 uncouples NMDA receptor-dependent enhancement of D1 signaling through the inhibition of D1-NMDA receptor association and has been demonstrated to physically interact with D2 receptors in cell cultures [130,176]. A growing number of postmortem human brain as well as preclinical studies have suggested an implication of PSD-95 in the pathophysiology of schizophrenia [177][178][179][180].…”

Section: Focus On Psd Scaffolding Proteins In Dopamine-glutamate Intementioning

confidence: 97%

MicroRNAs in Schizophrenia: Implications for Synaptic Plasticity and Dopamine–Glutamate Interaction at the Postsynaptic Density. New Avenues for Antipsychotic Treatment Under a Theranostic Perspective

et al. 2014

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Despite dopamine-glutamate aberrant interaction that has long been considered a relevant landmark of psychosis pathophysiology, several aspects of these two neurotransmitters reciprocal interaction remain to be defined. The emerging role of postsynaptic density (PSD) proteins at glutamate synapse as a molecular "lego" making a functional hub where different signals converge may add a new piece of information to understand how dopamine-glutamate interaction may work with regard to schizophrenia pathophysiology and treatment. More recently, compelling evidence suggests a relevant role for microRNA (miRNA) as a new class of dopamine and glutamate modulators with regulatory functions in the reciprocal interaction of these two neurotransmitters. Here, we aimed at addressing the following issues: (i) Do miRNAs have a role in schizophrenia pathophysiology in the context of dopamine-glutamate aberrant interaction? (ii) If miRNAs are relevant for dopamine-glutamate interaction, at what level this modulation takes place? (iii) Finally, will this knowledge open the door to innovative diagnostic and therapeutic tools? The biogenesis of miRNAs and their role in synaptic plasticity with relevance to schizophrenia will be considered in the context of dopamine-glutamate interaction, with special focus on miRNA interaction with PSD elements. From this framework, implications both for biomarkers identification and potential innovative interventions will be considered.

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Section: Focus On Psd Scaffolding Proteins In Dopamine-glutamate Intementioning

confidence: 97%

MicroRNAs in Schizophrenia: Implications for Synaptic Plasticity and Dopamine–Glutamate Interaction at the Postsynaptic Density. New Avenues for Antipsychotic Treatment Under a Theranostic Perspective

et al. 2014

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“…HEK293 membrane P2 fractions were prepared using the method described previously (Sun et al, 2009). In brief, cells were collected and lysed in hypotonic buffer [5 mM Tris-HCl and 2 mM EDTA (pH 7.4)] containing a protease inhibitor mixture (Sigma-Aldrich) and were sonicated three times for 18 seconds.…”

Section: Methodsmentioning

confidence: 99%

SKF83959 Is a Potent Allosteric Modulator of Sigma-1 Receptor

et al. 2013

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-2,3,4,5-tetrahydro-1H-3-benzazepine), an atypical dopamine receptor-1 (D 1 receptor) agonist, has shown many D 1 receptor-independent effects, such as neuroprotection, blockade of Na 1 channel, and promotion of spontaneous glutamate release, which resemble the effects of the sigma-1 receptor activation. In the present work, we explored the potential modulation of SKF83959 on the sigma-1 receptor. The results indicated that SKF83959 dramatically promoted the binding of 3 H(1)-pentazocine (a selective sigma-1 receptor agonist) to the sigma-1 receptor in brain and liver tissues but produced no effect on 3 H-progesterone binding (a sigma-1 receptor antagonist). The saturation assay and the dissociation kinetics assay confirmed the allosteric effect. We further demonstrated that the SKF83959 analogs, such as SCH22390 [(R)-(1)-7-chloro-8-hydroxy-3-methyl-1-phenyl-2,3,4,5-tetrahydro-1H-3-benzazepine hydrochloride] and SKF38393 [(+/-)-1-phenyl-2,3,4,5-tetrahydro-(1H)-3-benzazepine-7,8-diol hydrobromide], also showed the similar allosteric effect on the sigma-1 receptor in the liver tissue but not in the brain tissue. Moreover, all three tested chemicals elicited no significant effect on 3 H-1,3-di(2-tolyl)-guanidine ( 3 H-DTG) binding to the sigma-2 receptor. The present data uncovered a new role of SKF83959 and its analogs on the sigma-1 receptor, which, in turn, may reveal the underlying mechanism for the D 1 receptor-independent effect of the drug.

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“…PSD-95 has also been reported to positively regulate dopamine 1 receptor (D 1 R) endocytosis and inhibit D 1 R-mediated cAMP formation (Zhang et al, 2007b). A more recent study suggests that PSD-95 contributes to D 1 R recycling and resensitization without influencing D 1 R-mediated Ga s activation (Sun et al, 2009). However, the methods and cellular contexts used to arrive at these conclusions in these various studies are not directly comparable.…”

Section: Gpcr-interacting Psd-95 Family Pdz Domain-mentioning

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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PSD-95 regulates D1 dopamine receptor resensitization, but not receptor-mediated Gs-protein activation

Cited by 25 publications

References 37 publications

MicroRNAs in Schizophrenia: Implications for Synaptic Plasticity and Dopamine–Glutamate Interaction at the Postsynaptic Density. New Avenues for Antipsychotic Treatment Under a Theranostic Perspective

MicroRNAs in Schizophrenia: Implications for Synaptic Plasticity and Dopamine–Glutamate Interaction at the Postsynaptic Density. New Avenues for Antipsychotic Treatment Under a Theranostic Perspective

SKF83959 Is a Potent Allosteric Modulator of Sigma-1 Receptor

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

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