Developmental and mature expression of full-length and truncated TrkB receptors in the rat forebrain.
The neurotrophins brain-derived neurotrophic factor (BDNF) and NT-4/5 exert their trophic effects on the nervous system via signaling through trkB receptors. These receptors occur as splice variants of the trkB gene that encodes a full-length receptor containing the signal transducing tyrosine kinase domain as well as truncated forms lacking this domain. Because the importance of the trkB isoforms for development and maturation of the nervous system is unknown, we have examined the expression of trkB receptor isoforms during development of the rat forebrain using 1) a sensitive ribonuclease protection assay to distinguish full-length and truncated trkB transcripts, 2) western blot analysis to characterize developmental changes in trkB proteins, and 3) immunohistochemistry to determine the cellular localization of trkB receptors. In the rat forebrain, adult mRNA levels for full-length trkB are reached by birth, whereas truncated trkB message does not peak until postnatal days 10-15. Western blot analysis indicates that full-length trkB protein is the major form during early development, whereas truncated trkB protein predominates in all forebrain regions of late postnatal and adult rats. These data also suggest that the glycosylation state of these receptors changes during postnatal maturation. TrkB immunoreactivity is present predominately within neurons, where it is localized to axons, cell soma, and dendrites. Strong dendritic immunostaining is particularly evident in certain neuronal populations, such as pyramidal neurons in the hippocampus and in layer V of the neocortex. The dendritic localization of trkB receptors supports the hypothesis that dendrites, as well as axons, are important sites for neurotrophin actions in the central nervous system.
Department of Cell Biology, Georgetown University Medical Center, Washington, DC 20007, USA.
R H
RH
Fryer
D R
DR
Kaplan
S C
SC
Feinstein
M J
MJ
Radeke
D R
DR
Grayson
L F
LF
Kromer
D000818:Animals; D001369:Axons / Q000378:metabolism; D003712:Dendrites / Q000378:metabolism; D005314:Embryonic and Fetal Development / Q000502:physiology; D005260:Female; D006624:Hippocampus / Q000378:metabolism; D007150:Immunohistochemistry; D009419:Nerve Tissue Proteins / Q000737:chemistry / Q000235:genetics*; D010446:Peptide Fragments / Q000235:genetics*; D016548:Prosencephalon / Q000196:embryology / Q000254:growth & development / Q000378:metabolism*; D014176:Protein Biosynthesis; D011499:Protein Processing, Post-Translational; D012333:RNA, Messenger / Q000096:biosynthesis*; D051381:Rats; D017207:Rats, Sprague-Dawley; D020801:Receptor, Ciliary Neurotrophic Factor; D017475:Receptors, Nerve Growth Factor / Q000737:chemistry / Q000235:genetics*; D014158:Transcription, Genetic
D009419:Nerve Tissue Proteins; D010446:Peptide Fragments; D012333:RNA, Messenger; D020801:Receptor, Ciliary Neurotrophic Factor; D017475:Receptors, Nerve Growth Factor