RGS (Regulators-of-G-Protein-Signaling) proteins are a family of substances functionally related to G protein receptors and are located intracellularly near receptors. They function to terminate the action of agonist stimulation at a linked G protein-coupled receptor. These proteins have been described largely in animal brain and have not yet been fully characterized in human tissue. Evidence of their relevance to human brain diseases, especially to schizophrenia, is scant. Because schizophrenia is an illness responsive to dopamine receptor blockade, and possibly associated with augmented dopamine release, all parts of the dopamine system which participate in dopaminergic signal transduction deserve examination for potential association with pathophysiology. Moreover, RGS-4 (one of over 20 RGS proteins) has already been implicated in schizophrenia by microarray data and in situ hybridization in frontal cortex from one (but not from all) laboratories doing unbiased expression analysis in schizophrenia. Thus, based on a rational hypothesis and based on one piece of experimental data, relevant RGS proteins deserve a comprehensive survey in schizophrenia. If, after this analysis, we identify a signal in the schizophrenia cases, of abnormal quantities or distribution of any of these four RGS proteins, we will gear-up for a full characterization of the functional defect in the illness. We request funding in this small grant application for an initial screen of the four RGS proteins most closely related to dopamine, their regional densities in the normal and schizophrenia tissue and any differences from normal in either protein levels (by immunohistochemistry) or in protein expression (by in situ hybridization and Western analysis. Because of our previous work in schizophrenia neurochemistry, we have existing tissue blocks from schizophrenia (on treatment drugs), schizophrenia (off-drug x 6 mo), and matched control cases to use for this analysis. Thus, we can accomplish this experiment in a timely manner.
| Erdely, Holly A; Tamminga, Carol A; Roberts, Rosalinda C et al. (2006) Regional alterations in RGS4 protein in schizophrenia. Synapse 59:472-9 |
| Erdely, Holly A; Lahti, Robert A; Lopez, Mary B et al. (2004) Regional expression of RGS4 mRNA in human brain. Eur J Neurosci 19:3125-8 |
