title: Down-regulation of the neurotrophin receptor TrkB following ligand binding. Evidence for an involvement of the proteasome and differential regulation of TrkA and TrkB.
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.
authors.affiliation: Max-Planck Institute of Neurobiology, Department of Neurobiochemistry, Am Klopferspitz 18A, 82152 Planegg-Martinsried, Germany.
authors.forename: M T
authors.initials: MT
authors.lastname: Sommerfeld
authors.forename: R
authors.initials: R
authors.lastname: Schweigreiter
authors.forename: Y A
authors.initials: YA
authors.lastname: Barde
authors.forename: E
authors.initials: E
authors.lastname: Hoppe
mesh_terms: D000818:Animals; D019208:Brain-Derived Neurotrophic Factor / Q000378:metabolism*; D002531:Cerebellum / Q000166:cytology; D003546:Cysteine Endopeptidases / Q000378:metabolism*; D015853:Cysteine Proteinase Inhibitors / Q000494:pharmacology; D015536:Down-Regulation; D008024:Ligands; D009097:Multienzyme Complexes / Q000378:metabolism*; D009154:Mutation; D020932:Nerve Growth Factor / Q000378:metabolism; D009474:Neurons / Q000502:physiology*; D046988:Proteasome Endopeptidase Complex; D011485:Protein Binding; D051381:Rats; D020917:Receptor, trkA / Q000378:metabolism; D020813:Receptor, trkB / Q000096:biosynthesis / Q000378:metabolism*; D020812:Receptor, trkC / Q000378:metabolism; D011993:Recombinant Fusion Proteins / Q000378:metabolism
chemical_list: D019208:Brain-Derived Neurotrophic Factor; D015853:Cysteine Proteinase Inhibitors; D008024:Ligands; D009097:Multienzyme Complexes; D011993:Recombinant Fusion Proteins; D020932:Nerve Growth Factor; D020917:Receptor, trkA; D020813:Receptor, trkB; D020812:Receptor, trkC; D003546:Cysteine Endopeptidases; D046988:Proteasome Endopeptidase Complex