Mouse astrocytes store and deliver brain-derived neurotrophic factor using the non-catalytic gp95trkB receptor.
A study of the brain-derived neurotrophic factor (BDNF)-binding capacity of pure astrocytes demonstrated that these cells bind and endocytose [125I]BDNF rapidly using the gp95trkB truncated receptor. A linear Scatchard plot indicated the presence of only one type of receptor that bound the ligand, with a low Kd of 1.24 x 10(-8) M. There were an average of 36,468 copies of this receptor on untreated astrocytes. Interestingly, the neurotrophin was not degraded intracellularly, as demonstrated by HPLC experiments. Furthermore, the stored molecule was released by a mechanism regulated by the extracellular BDNF concentration as a bioactive neurotrophic molecule that supports neuron survival, in a time- and temperature-dependent manner. The data demonstrate that astrocytes exert an active role in the bioavailability of this neurotrophin, which is further enhanced in an inflammatory-like situation induced experimentally in culture using interferon-gamma.
Rubio
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Department of Neuroimmunology, Instituto Cajal, CSIC, Madrid, Spain.
D000818:Animals; D001253:Astrocytes / Q000378:metabolism*; D015152:Blotting, Northern; D019208:Brain-Derived Neurotrophic Factor / Q000378:metabolism*; D002384:Catalysis; D002478:Cells, Cultured; D002851:Chromatography, High Pressure Liquid; D005727:Ganglia, Spinal / Q000166:cytology / Q000378:metabolism; D051379:Mice; D008807:Mice, Inbred BALB C; D009474:Neurons / Q000378:metabolism; D016133:Polymerase Chain Reaction; D012636:Secretory Rate
D019208:Brain-Derived Neurotrophic Factor