Receptor-mediated endocytosis of transthyretin by ependymoma cells.
Transthyretin (TTR) is involved in the transport of thyroxine (T4) and retinol-binding protein (RBP) in cerebrospinal fluid (CSF) and serum. TTR is secreted in the CSF by the epithelial cells of choroid plexus. The binding of [(125)I]TTR to cultured ependymoma cells which form the brain cerebrospinal barrier, was studied to determine whether these cells carry receptor(s) for TTR. TTR was bound by ependymoma cells in a time-dependent manner reaching equilibrium within 2 h. Scatchard analysis was consistent with a single class of high-affinity binding sites with a K(d) of approximately 18 nM. Saturable high-affinity binding of human TTR has previously been described in rat primary hepatocytes and human renal adenocarcinoma, neuroblastoma, hepatoma and astrocytoma cells, and also transformed lung cells. Endocytosis of fluorescent or biotinylated TTR was observed in ependymoma cells in cytoplasmic vesicles but TTR did not colocalize with clathrin in endocytic coated vesicles. Endocytosis of TTR was inhibited by high sucrose concentration (0.45 M). Finally, ligand blotting and chemical-linking experiments revealed the presence of a approximately 100 kDa putative TTR receptor on the ependymoma cell membrane. Receptor binding of TTR provides a potential mechanism for the delivery of T4 within the central nervous system.
Kuchler-Bopp
S
S
Laboratoire de Neurobiologie Moléculaire des Interactions Cellulaires, 11, rue Humann, 67085 cedex, Strasbourg, France. sabine.kochler-bopp@medecine.u-strasbg.fr
Dietrich
J B
JB
Zaepfel
M
M
Delaunoy
J P
JP
D000818:Animals; D001692:Biological Transport / Q000502:physiology; D015152:Blotting, Northern; D001932:Brain Neoplasms; D002461:Cell Line, Transformed / Q000737:chemistry / Q000378:metabolism / Q000648:ultrastructure; D004705:Endocytosis / Q000502:physiology*; D004805:Ependyma / Q000166:cytology; D004806:Ependymoma; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D007457:Iodine Radioisotopes; D051379:Mice; D008822:Mice, Transgenic; D008854:Microscopy, Electron; D011228:Prealbumin / Q000235:genetics / Q000493:pharmacokinetics*; D012333:RNA, Messenger / Q000032:analysis; D051381:Rats; D017457:Receptors, Albumin / Q000032:analysis / Q000378:metabolism
D007457:Iodine Radioisotopes; D011228:Prealbumin; D012333:RNA, Messenger; D017457:Receptors, Albumin; C091986:transthyretin receptor