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 phosphatidylinositol (GPI) adduct is constitutively expressed in some transformed 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, the GPI-FBP in the liver, kidney, and brain of rats on control and folate-deficient (FD) diets was measured. The GPI-FBP in the kidney of FD rats decreased significantly in contrast to the upregulation of this protein in cultured 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 deficiency. This decrease of the GPI-FBP appears to result from its proteolysis, similar to the enzymatic degradation of the apoprotein that occurs in vitro. Because the GPI-FBP is on the brush borders of the proximal renal tubules and provides for the reabsorption of folate, this function diminishes when the protein decreases in folate deficiency.
da Costa
M
M
Division of Hematology/Oncology, Department of Medicine, Health Science Center at Brooklyn, State University of New York, Brooklyn, New York 11203, USA.
Rothenberg
S P
SP
Sadasivan
E
E
Regec
A
A
Qian
L
L
D000818:Animals; D001921:Brain / Q000378:metabolism; D002352:Carrier Proteins / Q000235:genetics / Q000378:metabolism*; D002460:Cell Line / Q000378:metabolism; D005260:Female; D058973:Folate Receptors, GPI-Anchored; D005494:Folic Acid Deficiency / Q000235:genetics / Q000378:metabolism*; D017261:Glycosylphosphatidylinositols / Q000235:genetics / Q000378:metabolism*; D007668:Kidney / Q000378:metabolism; D007684:Kidney Tubules / Q000378:metabolism*; D008099:Liver / Q000378:metabolism; D008297:Male; D010447:Peptide Hydrolases / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D011956:Receptors, Cell Surface; D012016:Reference Values; D014158:Transcription, Genetic; D015854:Up-Regulation
D002352:Carrier Proteins; D058973:Folate Receptors, GPI-Anchored; D017261:Glycosylphosphatidylinositols; D011956:Receptors, Cell Surface; D010447:Peptide Hydrolases