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.
Glass
David J
DJ
Regeneron Pharmaceuticals, Inc., Tarrytown, New York 10591.
Nye
Steven H
SH
Hantzopoulos
Petros
P
Macchi
Mary J
MJ
Squinto
Stephen P
SP
Goldfarb
Mitchell
M
Yancopoulos
George D
GD
D000818:Animals; D019208:Brain-Derived Neurotrophic Factor; D002455:Cell Division / Q000187:drug effects; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects; D004261:DNA Replication / Q000187:drug effects; D005347:Fibroblasts / Q000166:cytology / Q000187:drug effects; D008562:Membrane Glycoproteins / Q000378:metabolism*; D051379:Mice; D009414:Nerve Growth Factors / Q000494:pharmacology*; D009419:Nerve Tissue Proteins / Q000494:pharmacology*; D020933:Neurotrophin 3; D011505:Protein-Tyrosine Kinases / Q000378:metabolism*; D020813:Receptor, trkB; D011956:Receptors, Cell Surface / Q000502:physiology; D017475:Receptors, Nerve Growth Factor; D011994:Recombinant Proteins / Q000494:pharmacology; D014162:Transfection
D019208:Brain-Derived Neurotrophic Factor; D008562:Membrane Glycoproteins; D009414:Nerve Growth Factors; D009419:Nerve Tissue Proteins; D020933:Neurotrophin 3; D011956:Receptors, Cell Surface; D017475:Receptors, Nerve Growth Factor; D011994:Recombinant Proteins; C064371:Ntrk2 protein, mouse; D011505:Protein-Tyrosine Kinases; D020813:Receptor, trkB