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J Neurochem
2013 Oct 01;1271:57-65. doi: 10.1111/jnc.12359.
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Arrestin-dependent but G-protein coupled receptor kinase-independent uncoupling of D2-dopamine receptors.
Celver J
,
Sharma M
,
Thanawala V
,
Christopher Octeau J
,
Kovoor A
.
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We reconstituted D2 like dopamine receptor (D2R) and the delta opioid receptor (DOR) coupling to G-protein gated inwardly rectifying potassium channels (K(ir)3) and directly compared the effects of co-expression of G-protein coupled receptor kinase (GRK) and arrestin on agonist-dependent desensitization of the receptor response. We found, as described previously, that co-expression of a GRK and an arrestin synergistically increased the rate of agonist-dependent desensitization of DOR. In contrast, only arrestin expression was required to produce desensitization of D2R responses. Furthermore, arrestin-dependent GRK-independent desensitization of D2R-K(ir)3 coupling could be transferred to DOR by substituting the third cytoplasmic loop of DOR with that of D2R. The arrestin-dependent GRK-independent desensitization of D2R desensitization was inhibited by staurosporine treatment, and blocked by alanine substitution of putative protein kinase C phosphorylation sites in the third cytoplasmic loop of D2R. Finally, the D2R construct in which putative protein kinase C phosphorylation sites were mutated did not undergo significant agonist-dependent desensitization even after GRK co-expression, suggesting that GRK phosphorylation of D2R does not play an important role in uncoupling of the receptor.
Appleyard,
Agonist-dependent desensitization of the kappa opioid receptor by G protein receptor kinase and beta-arrestin.
1999, Pubmed,
Xenbase
Appleyard,
Agonist-dependent desensitization of the kappa opioid receptor by G protein receptor kinase and beta-arrestin.
1999,
Pubmed
,
Xenbase
Celver,
Distinct domains of the mu-opioid receptor control uncoupling and internalization.
2004,
Pubmed
,
Xenbase
Celver,
RGS9-2 mediates specific inhibition of agonist-induced internalization of D2-dopamine receptors.
2010,
Pubmed
,
Xenbase
Cho,
Agonist-induced endocytosis and receptor phosphorylation mediate resensitization of dopamine D(2) receptors.
2010,
Pubmed
DeWire,
Beta-arrestins and cell signaling.
2007,
Pubmed
Galliera,
beta-Arrestin-dependent constitutive internalization of the human chemokine decoy receptor D6.
2004,
Pubmed
Gimenez,
Role of receptor-attached phosphates in binding of visual and non-visual arrestins to G protein-coupled receptors.
2012,
Pubmed
Gurevich,
Arrestins as multi-functional signaling adaptors.
2008,
Pubmed
Gurevich,
G protein-coupled receptor kinases: more than just kinases and not only for GPCRs.
2012,
Pubmed
Gurevich,
The structural basis of arrestin-mediated regulation of G-protein-coupled receptors.
2006,
Pubmed
Gurevich,
The molecular acrobatics of arrestin activation.
2004,
Pubmed
Ito,
Sequestration of dopamine D2 receptors depends on coexpression of G-protein-coupled receptor kinases 2 or 5.
1999,
Pubmed
Jin,
Distinct domains of the CB1 cannabinoid receptor mediate desensitization and internalization.
1999,
Pubmed
,
Xenbase
Kearn,
Concurrent stimulation of cannabinoid CB1 and dopamine D2 receptors enhances heterodimer formation: a mechanism for receptor cross-talk?
2005,
Pubmed
Key,
N-formyl peptide receptor phosphorylation domains differentially regulate arrestin and agonist affinity.
2003,
Pubmed
Kovoor,
Mu and delta opioid receptors are differentially desensitized by the coexpression of beta-adrenergic receptor kinase 2 and beta-arrestin 2 in xenopus oocytes.
1997,
Pubmed
,
Xenbase
Kovoor,
Agonist-induced desensitization of the mu opioid receptor-coupled potassium channel (GIRK1).
1995,
Pubmed
,
Xenbase
Kovoor,
Gi Irks GIRKs.
2002,
Pubmed
Lan,
A dopamine D2 receptor mutant capable of G protein-mediated signaling but deficient in arrestin binding.
2009,
Pubmed
Missale,
Dopamine receptors: from structure to function.
1998,
Pubmed
Mukherjee,
Aspartic acid 564 in the third cytoplasmic loop of the luteinizing hormone/choriogonadotropin receptor is crucial for phosphorylation-independent interaction with arrestin2.
2002,
Pubmed
Namkung,
Protein kinase C mediates phosphorylation, desensitization, and trafficking of the D2 dopamine receptor.
2004,
Pubmed
Namkung,
G protein-coupled receptor kinase-mediated phosphorylation regulates post-endocytic trafficking of the D2 dopamine receptor.
2009,
Pubmed
Namkung,
G protein-coupled receptor kinase-2 constitutively regulates D2 dopamine receptor expression and signaling independently of receptor phosphorylation.
2009,
Pubmed
Neve,
Dopamine receptor signaling.
2004,
Pubmed
Pak,
Agonist-induced, G protein-dependent and -independent down-regulation of the mu opioid receptor. The receptor is a direct substrate for protein-tyrosine kinase.
1999,
Pubmed
Qiu,
Mu-opioid receptor desensitization: role of receptor phosphorylation, internalization, and representation.
2003,
Pubmed
Rascol,
Dyskinesia: L-dopa-induced and tardive dyskinesia.
2001,
Pubmed
Rasmussen,
Internalization of the human CRF receptor 1 is independent of classical phosphorylation sites and of beta-arrestin 1 recruitment.
2004,
Pubmed
Reiter,
Molecular mechanism of β-arrestin-biased agonism at seven-transmembrane receptors.
2012,
Pubmed
Remington,
Understanding antipsychotic "atypicality": a clinical and pharmacological moving target.
2003,
Pubmed
Seeman,
Psychosis pathways converge via D2high dopamine receptors.
2006,
Pubmed
Shapira,
Divers pathways mediate delta-opioid receptor down regulation within the same cell.
2001,
Pubmed
Thibault,
Neurotensin triggers dopamine D2 receptor desensitization through a protein kinase C and beta-arrestin1-dependent mechanism.
2011,
Pubmed
Xiang,
Heterologous activation of protein kinase C stimulates phosphorylation of delta-opioid receptor at serine 344, resulting in beta-arrestin- and clathrin-mediated receptor internalization.
2001,
Pubmed
