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Synthesis of transthyretin by the ependymal cells of the subcommissural organ

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Abstract

Transthyretin (TTR) is a protein involved in the transport of thyroid hormones in blood and cerebrospinal fluid (CSF). The only known source of brain-produced TTR is the choroid plexus. In the present investigation, we have identified the subcommissural organ (SCO) as a new source of brain TTR. The SCO is an ependymal gland that secretes glycoproteins into the CSF, where they aggregate to form Reissner’s fibre (RF). Evidence exists that the SCO also secretes proteins that remain soluble in the CSF. To investigate the CSF-soluble compounds secreted by the SCO further, antibodies were raised against polypeptides partially purified from fetal bovine CSF. One of these antibodies (against a 14-kDa compound) reacted with secretory granules in cells of fetal and adult bovine SCO, organ-cultured bovine SCO and the choroid plexus of several mammalian species but not with RF. Western blot analyses with this antibody revealed two polypeptides of 14 kDa and 40 kDa in the bovine SCO, in the conditioned medium of SCO explants, and in fetal and adult bovine CSF. Since the monomeric and tetrameric forms of TTR migrate as bands of 14 kDa and 40 kDa by SDS-polyacrylamide gel electrophoresis, a commercial preparation of human TTR was run, with both bands being reactive with this antibody. Bovine SCO was also shown to synthesise mRNA encoding TTR under in vivo and in vitro conditions. We conclude that the SCO synthesises TTR and secretes it into the CSF. Colocalisation studies demonstrated that the SCO possessed two populations of secretory cells, one secreting both RF glycoproteins and TTR and the other secreting only the former. TTR was also detected in the SCO of bovine embryos suggesting that this ependymal gland is an important source of TTR during brain development.

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References

  • Achen MG, Harms PJ, Thomas T, Richardson SJ, Wettenhall REH, Schreiber G (1992) Protein synthesis at the blood-brain barrier: the major protein secreted by amphibian choroid plexus is a lipocalin. J Biol Chem 267:23170–23174

    Google Scholar 

  • Achen MG, Duan W, Petterson TM, Harms PJ, Richardson SJ, Lawrence MC, Wettenhall REH, Aldred AR, Schreiber G (1993) Transthyretin gene expression in choroid plexus first evolved in reptiles. Am J Physiol 265:R982–R989

    Google Scholar 

  • Anderson GW (2001) Thyroid hormones and the brain. Front Neuroendocrinol 22:1–17

    Google Scholar 

  • Bellovino D, Moritomo T, Pisaniello A, Gaetani S (1998) In vitro and in vivo studies on transthyretin oligomerization. Exp Cell Res 243:101–112

    Google Scholar 

  • Blake C, Geisow M, Oatley S, Rerat B, Rerat C (1978) Structure of prealbumin: secondary, tertiary and quaternary interactions determined by Fourier refinement at 1,8. J Mol Biol 121:339–356

    Google Scholar 

  • Cozzani C, Hartmann B (1980) Preparation of antibodies specific to choline acetyltransferase from bovine caudate nucleus and immunohistochemical localization of the enzyme. Proc Natl Acad Sci USA 77:7453–7457

    Google Scholar 

  • Dickson PW, Aldred AR, Maarley PD, Bannister D, Schreiber G (1986) Rat choroid plexus specializes in the synthesis and secretion of transthyretin (prealbumin)—regulation of transthyretin synthesis in choroid plexus in independent from that in liver. J Biol Chem 261:3475–3478

    Google Scholar 

  • Divino CM, Schussler GC (1990) Receptor-mediated uptake and internalization of transthyretin. J Biol Chem 265:1425–1429

    Google Scholar 

  • Dussault JH, Ruel J (1987) Thyroid hormone and brain development. Annu Rev Physiol 49:321–334

    Google Scholar 

  • Episkopou V, Maeda S, Nishiguchi S, Shimada K, Gaitanaris GA, Gottesman ME, Robertson JE (1993) Disruption of the transthyretin gene results in mice with depressed level of plasma retinol and thyroid hormone. Proc Natl Acad Sci USA 90:2375–2379

    Google Scholar 

  • Fernández-Llebrez P, Pérez-Figares JM, Becerra J, Perez J, Marín-Girón F (1984) Morphological evidence for the presence of two cell types in the ependyma of the subcommissural organ of the snake, Natrix maura. Cell Tissue Res 238:407–409

    Google Scholar 

  • Fung W, Thomas T, Dickson P, Aldred A, Milland J, Dziadek M, Power B, Hudson P, Schreiber G (1988) Structure and expression of the rat transthyretin (prealbumin) gene. J Biol Chem 263:480–488

    Google Scholar 

  • González CB, Rodríguez EM (1980) Ultrastructure and immunocytochemistry of neurons in the supraoptic and paraventricular nuclei of the lizard Liolaemus cyanogaster. Evidence for the intracisternal location of the precursor of neurophysin. Cell Tissue Res 207:463–477

    Google Scholar 

  • Hofer H (1959) Zur Morphologie der circumventriculären Organe des Zwischenhirns der Säugetiere. Verh Dtsch Zool Ges 22:202–251

    Google Scholar 

  • Laemmli UK (1970) Cleavage of structural proteins during the assembly of the head of bacteriophage T4. Nature 227:680

    Google Scholar 

  • Larsen N, Kirkpatrick B (1996) Seven genes from human chromosome 18 map to chromosome 24 in the bovine. Cytogenet Cell Genet 73:184–186

    Google Scholar 

  • Lauder JM, Bloom FE (1974) Ontogeny of monoamine neurons in the locus coeruleus, raphe nuclei and substantia nigra of the rat. I. Cell differentiation. J Comp Neurol 155:469–481

    Google Scholar 

  • Mendel CM (1989) The free hormone hypothesis: a physiologically based mathematical model. Endocr Rev 10:232–274

    Google Scholar 

  • Mendes M, Joao M (2001) Internalization of transthyretin. Evidence of a novel yet unidentified receptor associated protein (RAP)-sensitive receptor. J Biol Chem 276:14420–14425

    Google Scholar 

  • Meiniel R, Molat JL, Duchier-Liris N, Meiniel A (1990) Ontogenesis of the secretory epithelium of the bovine subcommissural organ. A histofluorescence study using lectins and monoclonal antibodies. Dev Brain Res 55:171–180

    Google Scholar 

  • Meiniel A, Meiniel R, Didier R, Creveaux I, Gobron S, Monnerie H, Dastugue B (1996) The subcommissural organ and Reissner’s fibre complex—an enigma in the central nervous system? Prog Histochem Cytochem 30:1–66

    Google Scholar 

  • Nualart F, Hein S, Rodríguez EM, Oksche A (1991) Identification and partial characterization of the secretory glycoproteins of the bovine subcommissural organ Reissner’s fiber complex. Evidence for the existence of two precursor forms. Mol Brain Res 11:227–238

    Google Scholar 

  • O’Farrel PZ, Goodman HM, O’Farrel PH (1977) High resolution two-dimensional electrophoresis of basic as well as acidic proteins. Cell 12:1133–1142

    Google Scholar 

  • Palha JA, Thompson M, Morreale G, Episkopou V, Gottesman M, Mascarenhas MJ (1997) Transthyretin is not essential for thyroxine to reach the brain and other tissue in transthyretin-null mice. Am J Physiol 272:E485–E493

    Google Scholar 

  • Pérez-Fígares JM, Jiménez A, Rodríguez EM (2001) Subcommissural organ, cerebrospinal fluid circulation and hydrocephalus. Microsc Res Tech 52:591–697

    Google Scholar 

  • Peruzzo B, Pérez J, Fernández-Llebrez P, Pérez-Figares JM, Rodríguez EM (1990) Ultrastructural immunocytochemistry and lectin histochemistry of the subcommissural organ in the snake Natrix maura with particular emphasis on its vascular and leptomeningeal projections. Histochemistry 93:269–277

    Google Scholar 

  • Pettersson T, Carlstrom A, Jornvall H (1987) Different types of microheterogeneity of human thyroxine-binding prealbumin. Biochemistry 26:4572–4583

    Google Scholar 

  • Pettersson T, Carlstrom A, Ehrenberg A, Jornvall H (1989) Transthyretin microheterogeneity and thyroxine binding are influenced by non-amino acid components and glutathione constituents. Biochem Biophys Res Commun 158:341–347

    Google Scholar 

  • Pettersson T, Ernstron U, Griffiths W, Sjovall J, Bergman T, Jornvall H (1995) Lutein associated with a transthyretin indicates carotenoid derivation and novel multiplicity of transthyretin ligands. FEBS Lett 365:23–26

    Google Scholar 

  • Reid DG, MacLachlan LK, Voylo M, Leeson PD (1989) A proton and fluorine-nuclear magnetic resonance and fluorescence study of the binding of some natural and synthetic thyromimetics to prealbumin (transthyretin). J Biol Chem 264:2013–2023

    Google Scholar 

  • Richter HG, Munoz RI, Millán CS, Guiñazú MF, Yulis CR, Rodríguez EM (2001) The floor plate cells from bovines express the mRNA encoding for SCO-spondin and its translation products. Mol Brain Res 93:137–147

    Google Scholar 

  • Rodríguez EM, Oksche A, Hein S, Rodríguez S, Yulis CR (1984a) Comparative immunocytochemical study of the subcommissural organ. Cell Tissue Res 237:427–441

    Google Scholar 

  • Rodríguez EM, Yulis R, Peruzzo B, Alvial G, Andrade R (1984b) Standardization of various applications of methacrylate embedding and silver methenamine for light and electron microscopy immunocytochemistry. Histochemistry 81:253–263

    Google Scholar 

  • Rodríguez EM, Garrido O, Oksche A (1990) Lectin histochemistry of the human fetal subcommissural organ. Cell Tissue Res 262:105–113

    Google Scholar 

  • Rodríguez EM, Oksche A, Hein S, Yulis CR (1992) Cell biology of the subcommissural organ. Int Rev Cytol 135:39–121

    Google Scholar 

  • Rodríguez EM, Jara P, Richter H, Montecinos H, Flandes B, Wiegand R, Oksche A (1993) Evidence of the release of CSF-soluble secretory material from the subcommissural organ, with particular reference to the situation in human. In: Oksche A, Rodríguez EM, Fernández-Llebrez P (eds) The subcommissural organ: an ependymal brain gland. Springer, Berlin Heidelberg New York, pp 121–131

    Google Scholar 

  • Rodríguez EM, Rodríguez S, Hein S (1998) The subcommissural organ. Microsc Res Tech 41:98–123

    Google Scholar 

  • Rodríguez EM, Oksche A, Montecinos H (2001) Human subcommissural organ, with particular emphasis on its secretory activity during the fetal life. Microsc Res Tech 52:573–590

    Google Scholar 

  • Schoebitz K, Garrido O, Heinrichs M, Speer L, Rodríguez EM (1986) Ontogenetic development of the chick and duck subcommissural organ. An immunocytochemical study. Histochemistry 84:31–40

    Google Scholar 

  • Schoebitz K, Rodríguez EM, Garrido O (1993) Ontogenetic development of the subcommissural organ with reference to the flexural organ. In: Oksche A, Rodríguez EM, Fernández-Llebrez P (eds) The subcommissural organ: an ependymal brain gland. Springer, Berlin Heidelberg New York, pp 41–49

    Google Scholar 

  • Schoebitz K, González C, Peruzzo B, Yulis CR, Rodríguez EM (2001) Organ culture of the bovine subcommissural organ. Evidence for synthesis and release of the secretory material. Microsc Res Tech 52:496–509

    Google Scholar 

  • Schreiber G (2002) The evolutionary and integrative roles of transthyretin in thyroid hormone homeostasis. J Endocrinol 175:61–73

    Google Scholar 

  • Soprano DR, Herbert J, Soprano KJ, Schon EA, Goodman DS (1985) Demonstration of transthyretin mRNA in the brain and other extrahepatic tissue in the rat. J Biol Chem 260:11793–11798

    Google Scholar 

  • Sternberger LA, Hardy PH Jr, Cuculis JJ, Meyer HG (1970) The unlabeled antibody enzyme method of immunohistochemistry. Preparation and properties of soluble antigen–antibody complex (horseradish-peroxidase–antiperoxidase) and its use in identification of spirochetes. J Histochem Cytochem 18:315–333

    Google Scholar 

  • Thomas T, Power B, Hudson P, Schreiber G, Dziadek M (1988) The expression of transthyretin mRNA in the developing rat brain. Dev Biol 128:415–427

    Google Scholar 

  • Towbin H, Staehelin T, Gordon J (1979) Electrophoretic transfer of proteins from polyacrylamide gels to nitrocellulose sheet: procedure and some applications. Proc Natl Acad Sci USA 53:4350–4354

    Google Scholar 

  • Walker GR, Feather KD, Davis PD, Hines KK (1995) Super Signal TM CL-HRP: a new enhanced chemiluminescent substrate for the development of the horseradish peroxide label in Western blotting applications. J NIH Res 7:76

    Google Scholar 

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Author notes

  1. H. A. Montecinos & T. Caprile

    Present address: Departamento de Biología Celular, Facultad de Ciencias Biológicas, Universidad de Concepción, Concepción, Chile

Authors and Affiliations

  1. Facultad de Medicina, Instituto de Histología y Patología, Universidad Austral de Chile, Casilla de Correo (P.O. Box) 567, Valdivia, Chile

    H. A. Montecinos, H. Richter, T. Caprile & E. M. Rodríguez

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  1. H. A. Montecinos
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  2. H. Richter
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  4. E. M. Rodríguez
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Correspondence to E. M. Rodríguez.

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Financial support was provided by grants 1030265 from Fondecyt, Chile, to E.M.R. and 201.035.002-1.0 DIUC to H.M.

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Montecinos, H.A., Richter, H., Caprile, T. et al. Synthesis of transthyretin by the ependymal cells of the subcommissural organ. Cell Tissue Res 320, 487–499 (2005). https://doi.org/10.1007/s00441-004-0997-0

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