Searching for specific binding sites of the secretory glycoproteins of the subcommissural organ

Abstract

The molecular organization of Reissner's fiber (RF), the structure of its proteins, and the permanent turnover of these proteins are all facts supporting the possibility that RF may perform multiple functions. There is evidence that CSF-soluble RF-glycoproteins may occur under physiological conditions. The present investigation was designed to investigate the probable existence within the CNS of specific binding sites for RF-glycoproteins. Three experimental protocols were used: (1) immunocytochemistry of the CNS of bovine fetuses using anti-idiotypic antibodies, raised against monoclonal antibodies developed against bovine RF-glycoproteins; (2) in vivo binding of the RF glycoproteins, perfusing into the rat CSF 125I-labeled RF-glycoproteins, or grafting SCO into a lateral ventricle of the rat; (3) in vitro binding of unlabeled RF-glycoproteins to rat and bovine choroid plexuses maintained in culture. One of the anti-idiotypic antibody generated by a Mab raised against RF-glycoproteins binds to choroidal cells. Furthermore, binding of RF-glycoproteins to the rat choroid plexus was obtained when: (1) the choroid plexus was cultured in the presence of unlabeled RF-glycoproteins; (2) the concentration of soluble RF-glycoproteins in the CSF was increased by isografting SCOs into a lateral ventricle; (3) radiolabeled glycoproteins were perfused into the ventricular CSF. This evidence suggests that the apical plasma membrane of the ependymal cells of the choroid plexus has specific binding sites for RF-glycoproteins, of unknown functional significance. The radiolabeled RF-glycoproteins perfused into the rat CSF also bound to the paraventricular thalamic nucleus, the floor of the Sylvian aqueduct and of the rostral half of the fourth ventricle, and the meninges of the brain and spinal cord. The labeling of the paraventricular thalamic nucleus points to a functional relationship between this nucleus and the SCO. The possibility that the SCO may be a component of the circadian timing system is discussed. Microsc.

Development of Hydrocephalus in Mice Expressing the Gi-Coupled GPCR Ro1 RASSL Receptor in Astrocytes

“…The SCO may also regulate CSF formation. Receptors for SCO glycoproteins are found on the choroid plexus (Miranda et al, 2001), suggesting that CSF production could be influenced by SCO activity. It would be interesting to determine whether any of these parameters are altered in Ro1 mice.…”

Msx1 disruption leads to diencephalon defects and hydrocephalus

“…Interestingly, the presence of binding sites for RF glycoproteins in the PVT has been demonstrated (Miranda et al, 2001). These results suggest that the dysfunctional secretory SCO of homozygotes is related to these neurohistological disorders, especially because the PVT does not express the Msx1 gene in normal conditions (or in KO mice).…”

“…Msx1 mutant mice displayed neither structural nor ultrastructural anomalies in the choroidal cells, nor in the tela choroidea (results not shown). However, alterations of the secretory activity or cerebrospinal fluid (CSF) reabsorption cannot be ruled out, taking into account (1) the strong Msx1 expression in these structures and the presence of specific binding sites for Reissner's fiber-glycoproteins in ependymal cells of the choroid plexus (Miranda et al, 2001), and (2) the ependymal detachment, which seems to be, in certain cases, the primary cause of hydrocephalus .…”

Reissner’s fiber formation depends on developmentally regulated factors extrinsic to the subcommissural organ

“…Hence, if floor plate and choroid plexus cells do not synthesize and release the apical AFRU-positive material, a specific binding of such glycoproteins to these cells might be suggested. Furthermore, Miranda et al (2001) have reported the binding of radiolabelled RF glycoproteins perfused into CSF to the mesencephalic floor plate cells. The same authors have found AFRU-positive material attached to choroidal cells in the following situations: (1) rat SCO grafted into lateral ventricle of rat brain (this increases the secretion of material into the CSF) and (2) in vitro co-culture experiments of SCO and choroid plexus explants.…”