A review of folate receptor alpha cycling and 5-methyltetrahydrofolate accumulation with an emphasis on cell models in vitro.

Folate receptor alpha (FRalpha), a glycosyl phosphatidylinositol linked protein with a great affinity for folic acid and some reduced folates such as 5-methyltetrahydrofolate and tetrahydrofolate is present on a limited number of epithelial cells, especially the kidney, placenta and choroid plexus. It is also over-expressed in many carcinomas. The receptor appears to remain membrane bound but cycles between the cell surface and an internal compartment. Its localization to detergent resistant membranes (lipid rafts) may be important to its cycling and indeed putative function to conserve folate in selected body compartments. Agents that disrupt the actin cytoskeleton such as cytochalasin D as well as phorbol myristic acid effect cycling of the receptor. The monkey kidney cell line, MA104, has proved to be a useful model for studying FRalpha cycling and 5-methyltetrahydrofolate accumulation. This chapter reviews much of this work and compares and contrasts it to studies of other cells, both normal and malignant.