MOLECULAR-CLONING OF RAT TRKC AND DISTRIBUTION OF CELLS EXPRESSING MESSENGER-RNAS FOR MEMBERS OF THE TRK FAMILY IN THE RAT CENTRAL-NERVOUS-SYSTEM

Tyrosine protein kinases trk, trkB and trkC are signal-transducing receptors for the neurotrophins nerve growth factor, brain-derived nerve growth factor, neurotrophin-3 and neurotrophin-4. Here we report on the isolation of cDNA fragments encoding a part of rat trk and trkB proteins, respectively, and characterization of a full-length cDNA clone encoding rat trkC. Cells expressing mRNAs for the different members of the trk family were identified in the rat central nervous system by in situ hybridization using oligonucleotide probes designed from the isolated cDNA sequences and complementary to mRNA sequences coding for the extracellular region of the receptors. The expression of trk mRNA was found to be restricted to neurons of the basal forebrain, caudate-putamen with features of cholinergic cells and to magnocellular neurons of several brainstem nuclei. In contrast, cells expressing trkB and trkC mRNAs were widely distributed in the brain. Areas expressing high levels of trkB or trkC mRNAs included olfactory formations, neocortex, hippocampus, thalamic and-hypothalamic nuclei, brainstem nuclei, cerebellum and spinal cord motoneurons. A similar distribution for trkB and trkC mRNAs was shown in most areas but each probe specific for these mRNAs also provided distinct labeling patterns in different subregions, layers and cells. Comparison between our data and previous analyses of cells expressing mRNAs for neurotrophins and the low-affinity nerve growth factor receptor suggests that different modes of action and different combinations of receptors mediate biological responses to neurotrophins in the adult rat brain.