A SCL4A10 gene product maps selectively to the basolateral plasma membrane of choroid plexus epithelial cells

Abstract

The choroid plexus epithelium of the brain ventricular system produces the majority of the cerebrospinal fluid and thereby defines the ionic composition of the interstitial fluid in the brain. The transepithelial movement of Na+ and water in the choroid plexus depend on a yet-unidentified basolateral stilbene-sensitive [Formula: see text]-[Formula: see text] uptake protein. Reverse transcriptase-polymerase chain reaction (RT-PCR) analysis revealed the expression in the choroid plexus of SLC4A10 mRNA, which encodes a stilbene-sensitive [Formula: see text]-[Formula: see text] transporter. Anti-COOH-terminal antibodies were developed to determine the specific expression and localization of this [Formula: see text]-[Formula: see text] transport protein. Immunoblotting demonstrated antibody binding to a 180-kDa protein band from mouse and rat brain preparations enriched with choroid plexus. The immunoreactive band migrated as a 140-kDa protein after N-deglycosylation, consistent with the predicted molecular size of the SLC4A10 gene product. Bright-field immunohistochemistry and immunoelectron microscopy demonstrated strong labeling confined to the basolateral plasma membrane domain of the choroid plexus epithelium. Furthermore, the stilbene-insensitive [Formula: see text]-[Formula: see text] cotransporter, NBCn1, was also localized to the basolateral plasma membrane domain of the choroid plexus epithelium. Hence, we propose that the SLC4A10 gene product and NBCn1 both function as basolateral [Formula: see text] entry pathways and that the SLC4A10 gene product may be responsible for the stilbene-sensitive [Formula: see text]-[Formula: see text] uptake that is essential for cerebrospinal fluid production.