Truncated TrkB mediates the endocytosis and release of BDNF and neurotrophin-4/5 by rat astrocytes and Schwann cells in vitro

• Published in: Brain research Vol. 871; no. 2; pp. 210 - 222
• Main Authors: Alderson, Ralph F, Curtis, Rory, Alterman, Andrea L, Lindsay, Ronald M, DiStefano, Peter S
• Format: Journal Article
• Language: English
• Published: London Elsevier B.V 21.07.2000; Amsterdam Elsevier; New York, NY
• Subjects: Animals; Astrocytes - cytology; Astrocytes - drug effects; Astrocytes - metabolism; Binding Sites - drug effects; Binding Sites - physiology; Biological and medical sciences; Body Temperature - physiology; Brain-Derived Neurotrophic Factor - drug effects; Brain-Derived Neurotrophic Factor - metabolism; Brain-Derived Neurotrophic Factor - pharmacology; Cells, Cultured; Endocytosis - drug effects; Endocytosis - physiology; Fundamental and applied biological sciences. Psychology; Glia cells; Hippocampus; Hippocampus - cytology; Hippocampus - drug effects; Hippocampus - metabolism; Iodine Radioisotopes; Isolated neuron and nerve. Neuroglia; Nerve Growth Factors - drug effects; Nerve Growth Factors - metabolism; Nerve Growth Factors - pharmacology; Neurotrophin; Radioligand Assay; Rats; Receptor, trkB - drug effects; Receptor, trkB - metabolism; Schwann Cells - cytology; Schwann Cells - drug effects; Schwann Cells - metabolism; Sciatic nerve; Vertebrates: nervous system and sense organs; Neurotrophin; LNGFR, low-affinity nerve growth factor receptor; BSA, bovine serum albumin; NGF, nerve growth factor; DSS, disuccinimidyl suberate; EDAC, 1-ethyl-3-[3-dimethylaminopropyl]-carbodiimide hydrochloride; NT-3, neurotrophin-3; NT-4/5, neurotrophin-4/5; BDNF, brain-derived neurotrophic factor; Development and regeneration; Glia cells; Hippocampus; Sciatic nerve; Rat; Neuroglia; Rodentia; Central nervous system; Astrocyte; In vitro; Vertebrata; Endocytosis; Mammalia; Schwann cell; Brain derived neurotrophic factor; Release; Brain (vertebrata)
• ISSN: 0006-8993; 1872-6240
• DOI: 10.1016/S0006-8993(00)02428-8

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.