Neurotrophic factor receptors and their signal transduction capabilities in rat astrocytes.
Until recently, astrocytes were not considered as sites for neurotrophic factor action. We show here that, both in vivo and in vitro, astrocytes express receptors for two separate families of neurotrophic factors. In the intact adult rat CNS, astrocytes express the extracellular domain of the neurotrophin receptor TrkB and, in a more restricted population, the low-affinity nerve growth factor receptor p75LNGFR. In the lesioned CNS, expression of the alpha component of the receptor for ciliary neurotrophic factor (CNTFR alpha) switches from a purely neuronal localization to cells in the glial scar at the edge of the wound. Using cultured hippocampal astrocytes as a model to address the functional status of these receptors, we have found only the truncated forms of TrkB and TrkC, which are incapable of signal transduction as measured by protein tyrosine phosphorylation or immediate early gene induction. In contrast, a fully functional CNTF receptor complex capable of signal transduction is present on cultured astrocytes. Thus, the neurotrophin receptors may act primarily to sequester or present the neurotrophins, whereas in the case of CNTF a functional response can be initiated within the astrocyte.
Rudge
J S
JS
Regeneron Pharmaceuticals, Inc., Tarrytown, New York 10591.
Li
Y
Y
Pasnikowski
E M
EM
Mattsson
K
K
Pan
L
L
Yancopoulos
G D
GD
Wiegand
S J
SJ
Lindsay
R M
RM
Ip
N Y
NY
D000818:Animals; D001253:Astrocytes / Q000502:physiology*; D002478:Cells, Cultured; D020934:Ciliary Neurotrophic Factor; D005260:Female; D016222:Fibroblast Growth Factor 2 / Q000494:pharmacology; D005786:Gene Expression Regulation / Q000187:drug effects; D017781:Genes, Immediate-Early / Q000187:drug effects; D015850:Interleukin-6 / Q000494:pharmacology; D007961:Leukocyte Migration-Inhibitory Factors / Q000494:pharmacology; D008297:Male; D008565:Membrane Proteins / Q000502:physiology; D009419:Nerve Tissue Proteins / Q000494:pharmacology / Q000502:physiology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D020794:Receptor Protein-Tyrosine Kinases / Q000502:physiology; D020801:Receptor, Ciliary Neurotrophic Factor; D020812:Receptor, trkC; D017978:Receptors, Growth Factor / Q000502:physiology*; D017475:Receptors, Nerve Growth Factor / Q000502:physiology; D011994:Recombinant Proteins / Q000096:biosynthesis; D015398:Signal Transduction; D015533:Transcriptional Activation
D020934:Ciliary Neurotrophic Factor; D015850:Interleukin-6; D007961:Leukocyte Migration-Inhibitory Factors; D008565:Membrane Proteins; D009419:Nerve Tissue Proteins; D020801:Receptor, Ciliary Neurotrophic Factor; D017978:Receptors, Growth Factor; D017475:Receptors, Nerve Growth Factor; D011994:Recombinant Proteins; C089191:neurotrophin 4(5) receptor; D016222:Fibroblast Growth Factor 2; D020794:Receptor Protein-Tyrosine Kinases; D020812:Receptor, trkC