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Renal Tubular Reabsorption of Folate Mediated by Folate Binding Protein 1

Henrik Birn^*, Ofer Spiegelstein, Erik I. Christensen^* and Richard H. Finnell

^* Department of Cell Biology, University of Aarhus, Aarhus, Denmark; and Institute of Biosciences and Technology, Texas A&M University System Health Science Center, Houston, Texas

Address correspondence to: Dr. Henrik Birn, Department of Cell Biology, Institute of Anatomy, University of Aarhus, University Park, Building 234, Aarhus C, Denmark, DK-8000. Phone: +45-8942-3051; Fax: +45-8619-8664; E-mail: hb{at}ana.au.dk

Renal tubular reabsorption of filtered folate is essential for the conservation and normal homeostasis of this important vitamin. Different molecular mechanisms have been implicated in epithelial folate transport, including folate receptors. Defective expression or antibody inactivation of these is associated with embryonic defects also correlated with low folate intake; however, their contribution to renal tubular folate reabsorption has not been established. With the use of targeted inactivation of the folate binding protein 1 (folbp1) and folate binding protein 2 (folbp2) genes in mice, the role of folate receptors in renal epithelial folate reabsorption was evaluated during low and normal folate intake. Inactivation of folbp1 was associated with (1) loss of ³H-folic acid binding to crude kidney membranes, (2) increase in renal folate clearance, and (3) increase in urinary excretion and decrease in renal uptake of injected ³H-methyltetrahydrofolate. No changes in renal folate handling were observed as a result of folbp2 inactivation. Thus, folbp1 is essential for normal renal tubular folate reabsorption, preventing excessive urinary folate loss. Folbp1 is heavily expressed in choroid plexus, yolk sac, and placenta, supporting a role of folbp1 in folate transport in other tissues. The greatest significance of folbp1 for renal folate uptake was observed at conditions of low folate intake, providing a possible explanation for the ability of folate supplementation to prevent developmental defects associated with folbp1 inactivation.

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