REGULATORS OF G-PROTEIN SIGNALING (RGS) PROTEINS - REGION-SPECIFIC EXPRESSION OF 9 SUBTYPES IN RAT-BRAIN

The recently discovered regulators of G-protein signaling (RGS) protei ns potently modulate the functioning of heterotrimeric G-proteins by s timulating the GTPase activity of G-protein alpha subunits. The mRNAs for numerous subtypes of putative RGS proteins have been identified in mammalian tissues, but little is known about their expression in brai n. We performed a systematic survey of the localization of mRNAs encod ing nine of these RGSs, RGS3-RGS11, in brain by in situ hybridization. Striking region-specific patterns of expression were observed. Five s ubtypes, RGS4, RGS7, RGS8, RGS9, and RGS10 mRNAs, are densely expresse d in brain, whereas the other subtypes (RGS3, RGS5, RGS6, and RGS11) a re expressed at lower density and in more restricted regions. RGS4 mRN A is notable for its dense expression in neocortex, piriform cortex, c audoputamen, and ventrobasal thalamus. RGS8 mRNA is highly expressed i n the cerebellar Purkinje cell layer as well as in several midbrain nu clei. RGS9 mRNA is remarkable for its nearly exclusive enrichment in s triatal regions. RGS10 mRNA is densely expressed in dentate gyrus gran ule cells, superficial layers of neocortex, and dorsal raphe. To asses s whether the expression of RGS mRNAs can be regulated, we examined th e effect of an acute seizure on levels of RGS7, RGS8, and RGS10 mRNAs in hippocampus. Of the three subtypes, changes in RGS10 levels were mo st pronounced, decreasing by similar to 40% in a time-dependent manner in response to a single seizure. These results, which document highly specific patterns of RGS mRNA expression in brain and their ability t o be regulated in a dynamic manner, support the view that RGS proteins may play an important role in determining the intensity and specifici ty of signaling pathways in brain as well as their adaptations to syna ptic activity.