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Publications (4)11.5 Total impact

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    ABSTRACT: GPR26 and GPR78 are orphan GPCRs (oGPCRs) that share 51% amino acid sequence identity and are widely expressed in selected tissues of the human brain as well as the developing and adult mouse brain. Investigation of the functional activity of GPR26 and GPR78 via expression in HEK293 cells showed that both proteins are constitutively active and coupled to elevated cAMP production. Accordingly, in yeast, GPR26 demonstrated apparent agonist-independent coupling to a chimeric Gpa1 protein in which the 5 C-terminal amino acids were from Galphas. A comparison of the proteins revealed an atypical glutamine residue in GPR78 in place of the conserved arginine residue (R3.50) in the so-called DRY box. Site-directed mutants R3.50 in GPR26 were constructed and retained their constitutive activity suggesting that these 2 receptors activate G proteins in a manner that is distinct from other group 1 GPCRs.
    No preview · Article · Jul 2007 · Biochimica et Biophysica Acta
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    ABSTRACT: This report describes the identification and characterization of the murine orphan GPCR, Gpr101. Both human and murine genes were localized to chromosome X. Similar to its human ortholog, murine Gpr101 mRNA was detected predominantly in the brain within discrete nuclei. A knowledge-restricted hidden Markov model-based algorithm, capable of accurately predicting G-protein coupling selectivity, indicated that both human and murine GPR101 were likely coupled to Gs. This prediction was supported by the elevation of cyclic AMP levels and the activation of a cyclic AMP response element-luciferase reporter gene in HEK293 cells over-expressing human GPR101. Consistent with this, over-expression of human GPR101 in a yeast-based system yielded an elevated, agonist-independent reporter gene response in the presence of a yeast chimeric Galphas protein. These results indicate that GPR101 participates in a potentially wide range of activities in the CNS via modulation of cAMP levels.
    No preview · Article · Jun 2006 · Brain Research
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    ABSTRACT: Members of the MRG family of G-protein coupled receptors (GPCRs) are expressed predominately in small diameter sensory neurons of the dorsal root ganglia (DRG) suggesting a possible role in nociception. However, the large expansion of this gene family in rodents, combined with the lack of strict rodent orthologs for many of the human MRG genes, limits the usefulness of rodent models to evaluate human MRG involvement in nociception. Furthermore, the high degree of similarity between related rodent Mrg genes suggests that pharmacological approaches to define the function of individual receptors will prove difficult. The creation of an animal model to examine human MRG function will, therefore, require the identification of human MRG orthologs in a non-rodent species. Here we report the identification of MRGD, MRGE, and several MRGX orthologs in the crab-eating macaque, Macaca fascicularis. Similar to their human counterparts, all isolated macaque genes were expressed in dorsal root ganglia neurons. In the case of macaque MrgX2 and MrgD, expression was co-localized with the known nociceptive neuronal markers, IB4, VR1, and SP. Although expression in DRG neurons was the prominent feature of this family, we also found that MrgE was expressed in numerous brain regions of macaque, mouse, and human.
    No preview · Article · Mar 2005 · Molecular Brain Research
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    ABSTRACT: We report here the isolation of a novel gene termed mGluR5R (mGluR5-related). The N-terminus of mGluR5R is highly similar to the extracellular domain of metabotropic glutamate receptor 5 (mGluR5) whereas the C-terminus bears similarity to the testis-specific gene, RNF18. mGluR5R is expressed in the human CNS in a coordinate fashion with mGluR5. Although the sequence suggests that mGluR5R may be a secreted glutamate binding protein, we found that when expressed in HEK293 cells it was membrane associated and not secreted. Furthermore, mGluR5R was incapable of binding the metabotropic glutamate receptor class I selective agonist, quisqualate. Although mGluR5R could not form disulfide-mediated covalent homodimers, it was able to form a homomeric complex, presumably through noncovalent interactions. mGluR5R also formed noncovalent heteromeric associations with an engineered construct of the extracellular domain of mGluR5 as well as with full-length mGluR5 and mGluR1alpha. The ability of mGluR5R to associate with mGluR1alpha and mGluR5 suggests that it may be a modulator of class I metabotropic glutamate receptor function.
    No preview · Article · Jan 2003 · Molecular Brain Research