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  4. Down-regulation of the neurotrophin receptor TrkB following ligand binding : evidence for an involvement of the proteasome and differential regulation of TrkA and TrkB
 
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Down-regulation of the neurotrophin receptor TrkB following ligand binding : evidence for an involvement of the proteasome and differential regulation of TrkA and TrkB

Date Issued
2000-01-01
Author(s)
Sommerfeld, M T
Schweigreiter, R
Barde, Y A  
Hoppe, E
DOI
10.1074/jbc.275.12.8982
Abstract
This study examines the mechanisms by which the tyrosine kinase receptor TrkB is down-regulated following binding of brain-derived neurotrophic factor (BDNF). In primary cultures of cerebellar granule neurons, BDNF-induced reduction of TrkB receptors was largely prevented by the addition of specific proteasome inhibitors. HN10 cells, a neuronal cell line that can be readily transfected, also showed a marked down-regulation of cell surface TrkB following BDNF exposure. In addition, we observed that prolonged exposure to nerve growth factor of TrkA-transfected cells did not lead to the down-regulation seen with BDNF and TrkB. TrkA and TrkB chimeric molecules were therefore expressed in HN10 cells and tested for ligand-induced regulation. These experiments led to the conclusion that the motives responsible for down-regulation are contained in the cytoplasmic domain of TrkB, and a short sequence in the juxtamembrane domain of TrkB was identified that confers nerve growth factor-induced down-regulation when inserted into TrkA.
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