Differential expression of TrkC catalytic and noncatalytic isoforms suggests that they act independently or in association.

ABSTRACT

Members of the trk gene family encode neurotrophin receptors. The trkC locus encodes multiple neurotrophin-3 catalytic and noncatalytic receptor isoforms. We report the molecular cloning and characterization of mouse cDNAs encoding two noncatalytic TrkC receptors novel isoforms designated as TrkC NC1 and TrkC NC2, the mouse homologue of the TrkC truncated form previously identified in rat (Tsoulfas et al. [1993] Neuron 10975-990; Valenzuela et al. [1993] Neuron 10963-974). We extensively analyzed the transcription pattern of these two noncatalytic isoforms and that of the catalytic isoforms by Northern blotting and in situ hybridization. We did not detect trkC NC1 transcripts in embryos, but we found that trkC NC1 expression is restricted to specific areas in adult brain. In contrast, trkC NC2 transcripts are readily detected early during embryogenesis and are expressed predominantly in adult brain and gonads. We also provide the first evidence for the existence of TrkC NC2 protein by using polyclonal antibodies that specifically recognize this isoform. By using in situ hybridization, we show for the first time that trkC NC2 transcripts are found in differentiating fields of maturing neurons and in mature neurons of laminar structures of adult brain. We also report a similarity of localization between trkC NC2 transcripts and markers of oligodendrocyte progenitors in the embryonic spinal cord. Furthermore, our results also show that trkC NC2 and trkC catalytic transcripts could be either codistributed (in the central and peripheral nervous system) or independently expressed, especially outside the nervous system. These results suggest that the TrkC NC2 isoform acts either independently or in association with its catalytic counterpart. Finally, we show that TrkC NC2 is expressed in dendrites of pyramidal neurons of hippocampus and cerebral cortex. We propose that this receptor is involved in proliferation of oligodendrocyte progenitors, neuronal differentiation, and synaptic plasticity and that it may also play a fundamental role in mediating neurotrophin-3 effects outside the nervous system.