Aug 1, 1986

Receptor-mediated folate accumulation is regulated by the cellular folate content

Proceedings of the National Academy of Sciences of the United States of America
B A Kamen, A Capdevila

Abstract

Cultured monkey kidney cells are shown to possess a cell-surface receptor that binds 5-methyltetrahydro[3',5',7,9-3H4]folic acid (5-methyltetrahydro[3H]folic acid) with high affinity (Kd = 3 nM at 4 degrees C). The cell-surface binding capacity for [3H]folic acid or [3H]methotrexate is equivalent to that for 5-methyltetrahydro[3H]folate, but the Kd values are 0.4 and 20 nM, respectively. These nonlabeled folates also inhibit cellular binding and accumulation of 5-methyltetrahydro[3H]folate, whereas specific moieties of folic acid (i.e., p-aminobenzoylglutamic acid, pteroic acid, and glutamic acid) had no effect. Surface-bound folate(s) can be released by incubation of the cells at pH 3.5. At 37 degrees C the bound material is slowly transferred into cells, where it becomes resistant to acid release. Within 4 hr the cells internalize about 3-4 times as much folate as is bound to the surface in the steady state. The amount of receptor activity increases markedly when cells are depleted of folate through growth in folate-depleted medium. Binding of folate was inhibited by an antibody raised against a soluble plasma folate-binding protein, suggesting that the cell-surface receptor and the circulating folate-binding protein are immu...Continue Reading

  • References4
  • Citations141
  • References4
  • Citations141

Citations

Mentioned in this Paper

Hormone Receptors, Cell Surface
5-methyltetrahydrofolate, calcium salt (1: 1), (L-Glu)-isomer
Tetrahydrofolates
FOLR1
Methotrexate, (DL)-Isomer
Carrier Proteins
Folic Acid, Sodium Salt
Folate Receptors, GPI-Anchored

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