FOLATE RECEPTORS TARGETED TO CLATHRIN-COATED PITS CANNOT REGULATE VITAMIN UPTAKE

Potocytosis is an endocytic process that is specialized for the intern alization of small molecules. Recent studies on the uptake of 5-methyl tetrahydrofolate by the folate receptor have suggested that the glycos yl-phosphatidylinositol anchor on this protein causes it to cluster an d be internalized by caveolae instead of coated pits. To test this hyp othesis directly, we have constructed a chimeric folate receptor that has the glycosyl-phosphatidylinositol anchor replaced with the transme mbrane domain and cytoplasmic tail of the low density lipoprotein rece ptor. The cells with wild-type receptors delivered 5-methyltetrahydrof olate to the cytoplasm more rapidly than did cells expressing the chim eric receptor, This suggests that efficient delivery to the cytoplasm depends on caveolae. In sharp contrast to cells with wild type folate receptors, cells internalizing folate by clathrin-coated pits were una ble to decrease vitamin uptake when they were either folate replete or confluent.