RBAT, related to L-cysteine transport, is localized to the microvilli of proximal straight tubules, and its expression is regulated in kidney by development.

Abstract

We have recently isolated a renal cDNA clone (rBAT) that induces amino acid transport in oocytes either as a component or as a specific activator of a system bo,(+)-like transporter. (Bertran, J., Werner, A., Moore, M. L., Stange, G., Markovich, D., Biber, J., Testar, X., Zorzano, A., Palacín, M., and Murer, H. (1992) Proc. Natl. Acad. Sci. U. S. A. 89, 5601-5605. In order to obtain additional information on the rBAT protein, we have investigated the cellular localization of rBAT and its expression during development in rat kidney. A polyclonal antibody raised against rBAT recognizes a specific protein band of approximately 90 kDa, which is highly enriched in rat renal brush border membranes. Immunofluorescence and immunoelectron microscopy studies demonstrated that rBAT is expressed in the microvilli domain of S3 epithelial cells (i.e. straight tubules). The onset of rBAT mRNA expression in kidney was detected during late fetal life. In keeping with this, induction in oocytes of L-cystine uptake due to fetal rBAT-related mRNA was approximately 10% of the induction obtained with rBAT-related mRNA from adult kidneys. rBAT mRNA levels were low in early postnatal life, and only at the end of lactation did they increase steeply, attaining approximately 50% of adult values after weaning. rBAT protein was undetectable in total membrane preparations of kidneys from fetuses and early neonates, weakly detected during lactation, and represented < 15% of adult values after weaning. The postnatal expression of rBAT and its specific location in the microvilli of epithelial cells from the S3 segment of the proximal tubule coincide with postnatal maturation of cystine resorption and with the site of high affinity resorption of cysteine in kidney. This is consistent with the involvement of rBAT in a b(o,+)-like high-affinity resorption system for cysteine in the proximal straight tubule of the nephron.