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Selective binding and internalisation by truncated receptors restrict the availability of BDNF during development
S Biffo1, N Offenhäuser, B D Carter
1Max-Planck Institute for Psychiatry, Department of Neurobiochemistry, Planegg-Martinsried, Germany.
Summary
Truncated trkB receptors in non-neuronal cells act as a barrier, binding and internalizing brain-derived neurotrophic factor (BDNF) to regulate its diffusion during chick embryo development.
Area of Science:
- Neuroscience
- Developmental Biology
- Molecular Biology
Background:
- The tyrosine kinase receptor trkB mediates brain-derived neurotrophic factor (BDNF) actions.
- Truncated trkB variants lacking kinase activity have unknown functions.
- Understanding truncated trkB is crucial for neurotrophin signaling.
Purpose of the Study:
- Investigate the role and expression of truncated trkB receptors.
- Determine the function of truncated trkB in chick embryo development.
- Elucidate the interaction of truncated trkB with BDNF.
Main Methods:
- Studied truncated trkB expression patterns in chick embryos using mRNA detection and in situ hybridization.
- Examined BDNF binding affinity and selectivity on frozen sections.
- Investigated BDNF internalization by dissociated leptomeningeal cells.
Main Results:
- Truncated trkB mRNA is expressed early in neurogenesis in non-neuronal cells (ependymal, leptomeningeal).
- These cells surround developing brain and spinal cord, and specific structures like the otic vesicle.
- Non-neuronal cells expressing truncated trkB bind and internalize BDNF with high affinity and selectivity.
Conclusions:
- Truncated trkB receptors form a selective barrier for BDNF.
- This barrier prevents BDNF diffusion and eliminates it via internalization.
- Suggests a novel regulatory mechanism for neurotrophin availability during development.