Synthesis of transthyretin by the ependymal cells of the subcommissural organ

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.

High Blood Pressure Effects on the Brain Barriers and Choroid Plexus Secretion

“…The TTR monomer (m) is synthesized in the CP cells and secreted into the CSF. Some authors have described that TTRm is also synthesized in the SCO cells and is secreted from here into the CSF [7][8][9]. In the results of the present work it was found that when using immunohistochemistry and western blot there is an increase of TTR in hypertensive rats with respect to the control in the CP, this finding could mean alterations in the TTR secretions by CP cells.…”

“…The permeability of the brain barriers can also be studied by using Transthyretin (TTR) and S-100β: TTR is a protein involved in the transport of thyroid hormones in blood and CSF, and transthyretin is expressed in CSF as a monomer of 14 kDa (TTRm) and a dimmer of 28 kDa (TTRd), and in blood as a tetramer of 55kDa (TTRt). The TTR is synthesized in the choroid plexus (CP) cells and subcommissural organ (SCO) cells and secreted into the CSF [7][8][9] and the S-100β is synthesized in the astroglial and Swans cells, and when there are alterations in the BBB, the S-100β passes into the blood vessels [9,10].…”

Separation of minor protein components from whey protein isolates by heparin affinity chromatography

“…This protein, which is synthesized by lactating mammary epithelial cells, is involved in growth inhibition and differentiation in mammary epithelial cells (Schaap, van der Vusse, & Glatz, 1998;Spitsberg & Gorewit, 2002). Transthyretin, which is synthesized in the liver and the choroid plexus, is involved in the transport of thyroid hormones in blood and cerebrospinal fluid (Montecinos, Richter, Caprile, & Rodríguez, 2005;Schreiber, 2002). Hoshi et al (1996) reported that the concentration of b2-microglobulin in bovine colostrum is about 90 mg mL À1 .…”

Physiological response of bovine subcommissural organ to endothelin 1 and bradykinin

“…The possibility that the heterogeneity in the [Ca 2+ ] i responses might partially be attributable to the existence of subpopulations of SCO cells must be borne in mind. Indeed, the SCO is composed of ependymal and hypendymal secretory cells (Rodríguez et al 1998); furthermore, two types of secretory ependymocytes exist in the bovine SCO, i.e., those producing RF glycoproteins and those producing RF glycoproteins and transthyretin (Montecinos et al 2005). Differences in the [Ca 2+ ] i -response pattern between subpopulations of particular cell types have been described; isolated human T cells express different calcium-response patterns, and the proportion of these response patterns is dependent on the subtype and differentiation status of the T cells, suggesting a correlation between a particular calcium response and T cell function (Arrol et al 2008).…”