Truncated TrkB mediates the endocytosis and release of BDNF and neurotrophin-4/5 by rat astrocytes and schwann cells in vitro.
Binding and cross-linking studies with radiolabeled neurotrophins demonstrate that cultured rat hippocampal astrocytes lack full-length TrkB, but do express high levels of truncated TrkB (tTrkB). In astrocytes and Schwann cells, tTrkB appears to have the novel function of mediating the endocytosis of neurotrophins into an acid-stable, Triton X-100 resistant intracellular pool that is released back into the medium in a temperature-dependent manner. Chloroquine treatment, trichloroacetic acid solubility, and sodium dodecyl sulphate-polyacrylamide gel electrophoresis (SDS-PAGE) analysis revealed that when incubated with astrocytes or Schwann cells for at least 48 h neither the intracellular nor the released neurotrophins were significantly degraded. The endocytosis and release of neurotrophins may represent a novel mechanism whereby neuroglia can regulate the local concentration of these neurotrophic factors for extended periods of time.
Alderson
R F
RF
Regeneron Pharmaceuticals Inc., 777 Old Saw Mill River Road, Tarrytown, NY 10591-6707, USA. ralph_alderson@hgsi.com
Curtis
R
R
Alterman
A L
AL
Lindsay
R M
RM
DiStefano
P S
PS
D000818:Animals; D001253:Astrocytes / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D001665:Binding Sites / Q000187:drug effects / Q000502:physiology; D001831:Body Temperature / Q000502:physiology; D019208:Brain-Derived Neurotrophic Factor / Q000187:drug effects / Q000378:metabolism* / Q000494:pharmacology; D002478:Cells, Cultured; D004705:Endocytosis / Q000187:drug effects / Q000502:physiology*; D006624:Hippocampus / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D007457:Iodine Radioisotopes; D009414:Nerve Growth Factors / Q000187:drug effects / Q000378:metabolism* / Q000494:pharmacology; D011869:Radioligand Assay; D051381:Rats; D020813:Receptor, trkB / Q000187:drug effects / Q000378:metabolism*; D012583:Schwann Cells / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*
D019208:Brain-Derived Neurotrophic Factor; D007457:Iodine Radioisotopes; D009414:Nerve Growth Factors; C071951:neurotrophin 5; D020813:Receptor, trkB; C073922:neurotrophin 4