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Differential expression of TrkC catalytic and noncatalytic isoforms suggests that they act independently or in
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 10:975-990; Valenzuela et al. [1993] Neuron 10:963-974). 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.
Insights
Researchers identified two new noncatalytic TrkC receptor isoforms, TrkC NC1 and TrkC NC2. TrkC NC2 is expressed during development and in adult brain and gonads, suggesting diverse roles in neuronal function.
Area of Science:
- Neuroscience
- Molecular Biology
- Genetics
Background:
- The trk gene family encodes neurotrophin receptors, with trkC locus producing multiple neurotrophin-3 receptor isoforms.
- Previous studies identified truncated TrkC forms in rats, but mouse homologues and their functions remained largely uncharacterized.
Purpose of the Study:
- To molecularly clone and characterize two novel noncatalytic TrkC receptor isoforms in mice, designated TrkC NC1 and TrkC NC2.
- To analyze the expression patterns and potential functions of these isoforms in the developing and adult nervous system and other tissues.
Main Methods:
- Molecular cloning of mouse cDNAs encoding TrkC NC1 and TrkC NC2.
- Northern blotting and in situ hybridization to analyze trkC NC1 and trkC NC2 transcription patterns.
- Western blotting using specific polyclonal antibodies to detect TrkC NC2 protein.
- Immunohistochemistry to examine TrkC NC2 localization in neurons and glial progenitors.
Main Results:
- Two novel noncatalytic mouse TrkC isoforms, TrkC NC1 and TrkC NC2, were identified and characterized.
- TrkC NC1 expression was restricted to specific adult brain areas, absent in embryos.
- TrkC NC2 transcripts were detected early in embryogenesis, predominantly in adult brain and gonads, and TrkC NC2 protein was confirmed.
- TrkC NC2 transcripts localized to differentiating and mature neurons, oligodendrocyte progenitors in the embryonic spinal cord, and dendrites of hippocampal and cortical pyramidal neurons.
- TrkC NC2 and catalytic trkC transcripts showed both codistribution and independent expression patterns.
Conclusions:
- The TrkC NC2 isoform exhibits distinct temporal and spatial expression patterns, suggesting roles in neuronal differentiation, proliferation of oligodendrocyte progenitors, and synaptic plasticity.
- TrkC NC2 may function independently or in conjunction with catalytic TrkC receptors.
- TrkC NC2 likely mediates neurotrophin-3 effects both within and outside the central nervous system.