Ectopic expression of a chimeric colony-stimulating factor-1/TrkB-receptor promotes CSF-1-dependent survival of cultured sympathetic neurons.
The regulation of the density of innervation and the promotion of survival of neurons are the original effects depending on neurotrophins. Here we analyse such effects evoked by trkB tyrosine kinase in transfected PC12 cells and transfected sympathetic neurons. In order to exclude the previously described modulation of trk kinase activity by the extracellular activation of the low-affinity p75 neurotrophin receptor, we applied a chimeric receptor approach: The extracellular domain of colony-stimulating factor-1 (CSF-1) receptor was fused to the transmembrane and cytoplasmic domain of the trkB tyrosine kinase receptor, allowing its selective activation by the heterologous ligand. Protein expression and CSF-1-induced tyrosine phosphorylation of the chimeric receptor protein was demonstrated in transfected COS cells. After stable transfection into nerve growth factor (NGF)-responsive PC12 cells, CSF-1 mediated the K252a-sensitive induction of fiber outgrowth. Furthermore, we were able to show by heterologous expression of the chimeric receptor, that activation of trkB tyrosine kinase activity is sufficient to promote survival of neurotrophin deprived sympathetic neurons.
Erdmann
K S
KS
Department of Molecular Neurobiochemistry, Ruhr-University Bochum, Germany.
Kaiser
A D
AD
Klinz
F J
FJ
Zhong
J
J
Krautwald
S
S
Heumann
R
R
D000320:Adrenergic Fibers / Q000187:drug effects / Q000378:metabolism; D000818:Animals; D019556:COS Cells; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D002642:Chick Embryo; D002522:Chlorocebus aethiops; D015870:Gene Expression; D008024:Ligands; D016173:Macrophage Colony-Stimulating Factor / Q000494:pharmacology; D009414:Nerve Growth Factors / Q000494:pharmacology; D009474:Neurons / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D016716:PC12 Cells; D010766:Phosphorylation; D051381:Rats; D020794:Receptor Protein-Tyrosine Kinases / Q000235:genetics* / Q000378:metabolism*; D020801:Receptor, Ciliary Neurotrophic Factor; D016186:Receptor, Macrophage Colony-Stimulating Factor / Q000235:genetics* / Q000378:metabolism*; D017475:Receptors, Nerve Growth Factor / Q000235:genetics* / Q000378:metabolism*; D011993:Recombinant Fusion Proteins / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction; D014162:Transfection; D014443:Tyrosine / Q000378:metabolism
D008024:Ligands; D009414:Nerve Growth Factors; D020801:Receptor, Ciliary Neurotrophic Factor; D017475:Receptors, Nerve Growth Factor; D011993:Recombinant Fusion Proteins; D014443:Tyrosine; D016173:Macrophage Colony-Stimulating Factor; D020794:Receptor Protein-Tyrosine Kinases; D016186:Receptor, Macrophage Colony-Stimulating Factor