BDNF-activated signal transduction in rat cortical glial cells.
Cortical glial cells in culture were found to be responsive to the neurotrophin brain-derived neurotrophic factor (BDNF), as evidenced by activation of multiple signal transduction processes. BDNF produced an increase in mitogen-activated protein (MAP) kinase tyrosine phosphorylation, MAP kinase activity, intracellular calcium concentration and c-fos expression in the glial cells. Only a subset of the glial cells responded to BDNF, as reflected in single-cell analysis of calcium transients and c-fos expression. BDNF had no detectable effect on glial mitotic activity, as measured by DNA synthesis. In parallel studies, nerve growth factor and neurotrophin-3 had no effect on signalling in these cultures. BDNF has previously been demonstrated to act via trkB receptors with a cytoplasmic tyrosine kinase domain (gp145trkB). Pretreatment of glial cultures with K252a, which at low concentrations specifically inhibits the trk tyrosine kinases, abolished BDNF effects on MAP kinase stimulation, suggesting that BDNF was acting through gp145trkB. However, subsequent studies showed that gp145trkB was expressed at extremely low levels in the cultures: gp145trkB mRNA transcripts could only be detected using the reverse transcription-polymerase chain reaction, and gp145trkB protein was not detected by either immunoblotting or immunocytochemistry. On the other hand, the glia expressed significantly higher levels of gp95trkB mRNA and protein, which represent truncated forms of trkB receptors lacking the tyrosine kinase domain. The results of these studies demonstrate that a subset of cultured CNS glia respond to BDNF with the activation of conventional signal transduction processes. The mechanism of BDNF-initiated signal transduction in glial cells most likely involves a relatively small number of gp145trkB receptors, but involvement of the more abundant truncated gp95trkB receptors cannot be excluded.
Roback
J D
JD
Department of Pathology, Albert Einstein College of Medicine, Bronx, NY 10461, USA.
Marsh
H N
HN
Downen
M
M
Palfrey
H C
HC
Wainer
B H
BH
D000818:Animals; D019208:Brain-Derived Neurotrophic Factor; D002118:Calcium / Q000378:metabolism; D002478:Cells, Cultured; D002540:Cerebral Cortex / Q000187:drug effects / Q000378:metabolism; D015870:Gene Expression; D007150:Immunohistochemistry; D009419:Nerve Tissue Proteins / Q000494:pharmacology*; D009457:Neuroglia / Q000187:drug effects*; D011505:Protein-Tyrosine Kinases / Q000378:metabolism; D016760:Proto-Oncogene Proteins c-fos / Q000378:metabolism*; D051381:Rats; D011919:Rats, Inbred Strains; D015398:Signal Transduction / Q000187:drug effects*; D013997:Time Factors
D019208:Brain-Derived Neurotrophic Factor; D009419:Nerve Tissue Proteins; D016760:Proto-Oncogene Proteins c-fos; D011505:Protein-Tyrosine Kinases; D002118:Calcium