TRKB MEDIATES BDNF/NT-3-DEPENDENT SURVIVAL AND PROLIFERATION IN FIBROBLASTS LACKING THE LOW AFFINITY NGF RECEPTOR

The neurotrophins (nerve growth factor [NGF], brain-derived neurotrophic factor [BDNF], neurotrophin-3 [NT-3], and neurotrophin-4 [NT-4]) have been defined by their ability to support neuronal survival. These factors utilize the Trk family of receptor tyrosine kinases, perhaps in conjunction with a second component known as the low affinity NGF receptor (LNGFR). Here we demonstrate that TrkB mediates survival and proliferation in response to both BDNF and NT-3 when expressed in a particular strain of NIH 3T3 fibroblasts, with BDNF the more potent ligand. Furthermore, the BDNF dose dependency displayed by these TrkB-expressing fibroblasts is similar to that required to support the survival of primary neurons. The LNGFR is not expressed in our fibroblast system, implying that this receptor is not essential for responses to physiological concentrations of the neurotrophins. We discuss our findings in the context of neurotrophin signaling pathways and mechanisms of neuronal cell death.