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Characterization of Gpr101 expression and G-protein coupling selectivity
Brian Bates1, Lynn Zhang, Stan Nawoschik
1Wyeth Research, Biological Technologies, 87 Cambridge Park Drive, Cambridge, MA 02140, USA. bbates@wyeth.com
Brain Research
|May 2, 2006
Summary
Researchers identified and characterized the G protein-coupled receptor 101 (GPR101), finding it primarily in the brain. GPR101 activation elevates cyclic AMP levels, suggesting a role in central nervous system activities.
Area of Science:
- Neuroscience
- Molecular Biology
- Genetics
Background:
- Orphan G protein-coupled receptors (GPCRs) represent a significant class of cell surface receptors with largely unknown functions.
- GPR101, a specific orphan GPCR, was previously identified but lacked detailed characterization.
Purpose of the Study:
- To identify and characterize the murine orphan GPCR, Gpr101.
- To determine the G-protein coupling selectivity and functional consequences of GPR101 activation.
Main Methods:
- Gene localization to chromosome X in both human and murine models.
- mRNA expression analysis in murine brain tissue.
- Bioinformatic prediction of G-protein coupling using a hidden Markov model.
- Functional assays in HEK293 cells and yeast-based systems to measure cyclic AMP (cAMP) levels and reporter gene activation.
Main Results:
- Murine and human GPR101 genes are located on chromosome X.
- Gpr101 mRNA is predominantly expressed in discrete nuclei within the murine brain.
- Bioinformatic analysis and experimental data indicate GPR101 couples to the Gs protein.
- Over-expression of GPR101 leads to elevated cAMP levels and reporter gene activation, independent of an agonist.
Conclusions:
- GPR101 is a Gs-coupled receptor predominantly expressed in the brain.
- GPR101 modulates cAMP levels, suggesting a role in various central nervous system (CNS) functions.