SELECTIVE BINDING AND INTERNALIZATION BY TRUNCATED RECEPTORS RESTRICTTHE 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 expres sed by a large variety of neurons during development, Truncated trkB m olecules lacking the tyrosine kinase domain have also been described, but their functions remain elusive, In order to gain insight into thei r role, we studied the pattern of expression and properties of these t runcated receptors in the chick embryo. mRNA coding for truncated trkB was detected already early during neurogenesis and in situ hybridisat ion experiments indicated that the expression was in non-neuronal cell s, as previously observed in the brain of adult rodents, Ependymal and leptomeningeal cells expressing high levels of truncated trkB were fo und to completely surround the developing brain and the spinal cord th roughout development, In the otic vesicle, mesenchymal cells expressin g truncated trkB surround cells producing brain-derive neurotrophic fa ctor, as well as neurons expressing trkB with its tyrosine kinase doma in, 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 r evealed that non-neuronal cells expressing truncated trkB bind brain-d erived neurotrophic factor with high affinity and selectivity. In addi tion, 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 efficien t and selective barrier preventing the diffusion of brain-derived neur otrophic factor and eliminating it by internalisation. This barrier is in place early during neurogenesis and might be necessitated by the m ultiplicity of developing structures producing brain-derived neurotrop hic factor, as well as by the large number of different neuronal popul ations responding to brain-derived neurotrophic factor.