trkB encodes a functional receptor for brain-derived neurotrophic factor and neurotrophin-3 but not nerve growth factor.

A variety of findings seem to functionally link brain-derived neurotrophic factor (BDNF) and neurotrophin-3 (NT-3), while distinguishing both of these factors from the third member of the neurotrophin family, nerve growth factor (NGF). Here we demonstrate that all three of these neuronal survival molecules bind similarly to the low affinity NGF receptor, but that BDNF and NT-3, unlike NGF, do not act via the high affinity NGF receptor. However, both BDNF and NT-3, but not NGF, bind to full-length and truncated forms of a receptor-like tyrosine kinase, trkB, for which no ligand had previously been identified. In addition to binding BDNF and NT-3, trkB can mediate functional responses to both of these neurotrophins when it is expressed in PC12 cells, although BDNF appears to be the more effective ligand. Thus trkB encodes an essential component of a functional receptor for BDNF and NT-3, but not for NGF. Further evidence predicts the existence of additional functional receptors for the neurotrophins.

Identification of functional receptors for ciliary neurotrophic factor on neuronal cell lines and primary neurons.

The lack of reagents or molecular probes specific for the ciliary neurotrophic factor (CNTF) receptor has hindered characterization of the molecular mechanism(s) by which CNTF influences the proliferation, survival, and differentiation of cells of the vertebrate nervous system. We have developed methods for the detection and separation of cells expressing CNTF receptors by using a variety of binding assays based on a genetically engineered CNTF molecule containing an "epitope tag" at its C-terminus. These assays have allowed us to identify several neuronal cell lines, as well as embryonic and adult neurons in primary cultures, that bind CNTF and functionally respond to CNTF by rapidly activating the transcription of immediate early primary response genes.