Proposed transepithelial pathway for albumin through choroid plexus epithelial cells.

<p><b>A.</b> Whole choroid plexus showing single layer of epithelial cells sitting on thick basement membrane (see also <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0033554#pone-0033554-g001" target="_blank"><b><u>Fig. 1C</u></b></a>). <b>B.</b> Illustration depicting the suggested routes of albumin from plasma into CSF across the choroid plexus epithelium. GYPA/C in the endothelial cells may deliver albumin to the basement membrane (1) from where it can be taken up into the plexus epithelium by GYPA/C or SPARC (2). From here albumin may travel along a SPARC-specific pathway through the tubulocisternal endoplasmic reticulum (3, and see C) and Golgi (4a), or via a VAMP-mediated pathway in vacuoles, lysosomes or multivesicular bodies (4b, and see panel C). On the apical surface of the plexus epithelium, GYPA/C may be involved in efflux of protein from the cell into the CSF of the ventricles (5), as validated by extensive GYPA immunoreactivity in embryonic plexus (<a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0033554#pone-0033554-g005" target="_blank"><b><u>Fig. 5A</u></b></a>). In the adult, the lack of immunoreactivity in the endoplasmic reticulum and Golgi (see <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0033554#pone-0033554-g005" target="_blank"><b><u>Fig. 5</u></b></a> and <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0033554#pone-0033554-g006" target="_blank"><b><u>Fig. 6</u></b></a>) along with increased expression of gene products for VAMP molecules (see <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0033554#pone-0033554-g003" target="_blank"><b><u>Fig. 3C</u></b></a>) suggest that the majority of transport possibly occurs via VAMP-mediated vesicular/lysosomal transport such as shown in (4b). <b>C.</b> Transmission electron micrograph of ultracryosection from E60 fetal sheep choroid plexus <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0033554#pone.0033554-Mllgrd3" target="_blank">[87]</a>. Immunolabelled human albumin 6 nm particles and sheep albumin 12 nm gold particles are shown to co-localise within the tubulocisternal endoplasmic reticulum. Abbreviations: CPEC, choroid plexus epithelial cell; CSF, cerebrospinal fluid; GYPA, glycophorin A; GYPC, glycophorin C; MVB, multivescicular body; TER, tubulocisternal endoplasmic reticulum. Scale bar: 0.2 µm in C.