Guanine nucleotide exchange factors CalDAG-GEFI and CalDAG-GEFII are colocalized in striatal projection neurons

CalDAG-GEFI and CalDAG-GEFII (identical to RasGRP) are novel, brain-enriche d guanine nucleotide exchange factors (GEFs) that can be stimulated by calc ium and diacylglycerol and that can activate small GTPases, including Ras a nd Rap1, molecules increasingly recognized as having signaling functions in neurons. Here, we show that CalDAG-GEFI and CalDAG-GEFII mRNAs, detected b y in situ hybridization analysis, have sharply contrasting forebrain-predom inant distributions in the mature brain: CalDAG-GEFI is expressed mainly in the striatum and olfactory structures and deep cortical layers, whereas Ca lDAG-GEFII is expressed widely in the forebrain. Within the striatum, howev er, the two CalDAG-GEF mRNAs have nearly identical distributions: they are coexpressed in striatal projection neurons that give rise to the direct and indirect pathways of the basal ganglia. Subcellular fractionation analysis of the substantia nigra with monoclonal antibodies against CalDAG-GEFI sug gests that CalDAG-GEFI protein is present not only in the cell bodies of st riatal projection neurons but also in their axons and axon terminals. These results suggest that the CalDAG-GEFs may be key intracellular regulators w hereby calcium and diacylglycerol signals can regulate cellular functions t hrough small GTPases in the basal ganglia circuits. J. Comp. Neurol. 437:39 8-407, 2001. (C) 2001 Wiley-Liss, Inc.