Distribution of ras guanyl releasing protein (RasGRP) mRNA in the adult rat central nervous system

In the nervous system, Ras signal transduction pathways are involved in cel lular differentiation, neuronal survival and synaptic plasticity. These pat hways can be modulated by Ras guanyl nucleotide exchange factors (Ras GEFs) , which activate Ras protein by catalyzing the exchange of GDP for GTP. Ras GRP, a recently discovered Ras GEF is expressed in brain as well as in T ce lls. In addition to the catalytic domain which catalyzes dissociation of Ra s-GDP, RasGRP has a pair of calcium-binding EF hands and a diacylglycerol b inding domain. The structure of RasGRP suggests that it serves to link calc ium and lipid messengers to Ras signaling pathways. We have used an RNase p rotection assay to detect RasGRP mRNA in various regions of the rat brain a nd we have determined the cellular distribution of RasGRP mRNA by in situ h ybridization. RasGRP mRNA is widely distributed and is present in both inte rneurons and projection neurons but not confined to any neuronal type or ne urotransmitter phenotype. The presence of RasGRP mRNA in archicortical neur ons suggests that this pathway may be important in phylogenetically older r egions of the CNS. The restriction of RasGRP mRNA to subsets of neurons sug gests that activation of Ras by RasGRP has a specific function in certain n euronal types. We did not detect RasGRP in glial cells.