Selective binding and internalisation by truncated receptors restrict the availability of BDNF during development.
The tyrosine kinase receptor trkB is thought to mediate the biological actions of brain-derived neurotrophic factor. This receptor is expressed by a large variety of neurons during development. Truncated trkB molecules lacking the tyrosine kinase domain have also been described, but their functions remain elusive. In order to gain insight into their role, we studied the pattern of expression and properties of these truncated receptors in the chick embryo. mRNA coding for truncated trkB was detected already early during neurogenesis and in situ hybridisation experiments indicated that the expression was in non-neuronal cells, as previously observed in the brain of adult rodents. Ependymal and leptomeningeal cells expressing high levels of truncated trkB were found to completely surround the developing brain and the spinal cord throughout development. In the otic vesicle, mesenchymal cells expressing truncated trkB surround cells producing brain-derived neurotrophic factor, as well as neurons expressing trkB with its tyrosine kinase domain. Non-neuronal cells were found not to express trkB mRNA coding for the tyrosine kinase domain. Studies with radioiodinated brain-derived neurotrophic factor performed on frozen sections of the chick embryo revealed that non-neuronal cells expressing truncated trkB bind brain-derived neurotrophic factor with high affinity and selectivity. In addition, experiments with dissociated leptomeningeal cells revealed that binding is rapidly followed by selective internalisation of the ligand. These results suggest that truncated trkB molecules form an efficient and selective barrier preventing the diffusion of brain-derived neurotrophic factor and eliminating it by internalisation.(ABSTRACT TRUNCATED AT 250 WORDS)
Biffo
S
S
Max-Planck Institute for Psychiatry, Department of Neurobiochemistry, Planegg-Martinsried, Germany.
Offenhäuser
N
N
Carter
B D
BD
Barde
Y A
YA
D017398:Alternative Splicing; D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D019208:Brain-Derived Neurotrophic Factor; D002490:Central Nervous System / Q000196:embryology*; D002642:Chick Embryo; D017931:DNA Primers; D017403:In Situ Hybridization; D008578:Meninges / Q000166:cytology / Q000378:metabolism; D008648:Mesoderm / Q000502:physiology; D008969:Molecular Sequence Data; D009024:Morphogenesis / Q000502:physiology; D009414:Nerve Growth Factors / Q000378:metabolism*; D009419:Nerve Tissue Proteins / Q000378:metabolism*; D010446:Peptide Fragments / Q000235:genetics / Q000378:metabolism; D016133:Polymerase Chain Reaction; D020794:Receptor Protein-Tyrosine Kinases / Q000235:genetics / Q000378:metabolism*; D020801:Receptor, Ciliary Neurotrophic Factor; D017475:Receptors, Nerve Growth Factor / Q000235:genetics / Q000378:metabolism*
D019208:Brain-Derived Neurotrophic Factor; D017931:DNA Primers; D009414:Nerve Growth Factors; D009419:Nerve Tissue Proteins; D010446:Peptide Fragments; D020801:Receptor, Ciliary Neurotrophic Factor; D017475:Receptors, Nerve Growth Factor; D020794:Receptor Protein-Tyrosine Kinases