Folate deficiency reduces the GPI-anchored folate-binding protein in rat renal tubules

A folate-binding protein (FBP) anchored to cell membranes by a glycosyl pho sphatidylinositol (GPI) adduct is constitutively expressed in some transfor med and cultured cell lines. Its expression is upregulated when these cells are grown in medium containing low folate, but whether this occurs in vivo with nutritional folate deficiency is unknown. To address this question, t he GPI-FBP in the liver, kidney, and brain of rats on control and folate-de ficient (FD) diets was measured. The GPI-FBP in the kidney of FD rats decre ased significantly in contrast to the upregulation of this protein in cultu red cells. Northern blot analysis and nuclear run-on assays indicated that transcription of the GPI-FBP gene in the kidney was not reduced by folate d eficiency. This decrease of the GPI-FBP appears to result from its proteoly sis, similar to the enzymatic degradation of the apoprotein that occurs in vitro. Because the GPI-FBP is an the brush borders of the proximal renal tu bules and provides for the reabsorption of folate. this function diminishes when the protein decreases in folate deficiency.