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Guanine nucleotide exchange factors CalDAG‐GEFI and CalDAG‐GEFII are colocalized in striatal projection neurons
Author(s) -
Toki Shinichiro,
Kawasaki Hiroaki,
Tashiro Nobutada,
Housman David E.,
Graybiel Ann M.
Publication year - 2001
Publication title -
journal of comparative neurology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.855
H-Index - 209
eISSN - 1096-9861
pISSN - 0021-9967
DOI - 10.1002/cne.1291
Subject(s) - neuroscience , guanine nucleotide exchange factor , striatum , basal ganglia , medicine , biology , gtpase , microbiology and biotechnology , dopamine , central nervous system
CalDAG‐GEFI and CalDAG‐GEFII (identical to RasGRP) are novel, brain‐enriched guanine nucleotide exchange factors (GEFs) that can be stimulated by calcium and diacylglycerol and that can activate small GTPases, including Ras and Rap1, molecules increasingly recognized as having signaling functions in neurons. Here, we show that CalDAG‐GEFI and CalDAG‐GEFII mRNAs, detected by in situ hybridization analysis, have sharply contrasting forebrain‐predominant distributions in the mature brain: CalDAG‐GEFI is expressed mainly in the striatum and olfactory structures and deep cortical layers, whereas CalDAG‐GEFII is expressed widely in the forebrain. Within the striatum, however, 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 suggests that CalDAG‐GEFI protein is present not only in the cell bodies of striatal projection neurons but also in their axons and axon terminals. These results suggest that the CalDAG‐GEFs may be key intracellular regulators whereby calcium and diacylglycerol signals can regulate cellular functions through small GTPases in the basal ganglia circuits. J. Comp. Neurol. 437:398–407, 2001. © 2001 Wiley‐Liss, Inc.