PMA alters folate receptor distribution in the plasma membrane and increases the rate of 5-methyltetrahydrofolate delivery in mature MA104 cells

Cheryl M. Lewis, Angela K. Smith, Charles Nguyen, Barton A. Kamen

Research output: Contribution to journalArticle

10 Scopus citations

Abstract

MA 104 cells (a monkey kidney cell line) can internalize 5- methyltetrahydrofolate via a receptor mediated process termed potocytosis. Uptake is initiated by binding to an external folate receptor which cycles to an internal, but membrane bound compartment. These two pools can be measured by determining the amount of [3H]ligand removed by an acid-saline wash, i.e. acid labile and acid resistant pools. When assayed in confluent nonmitotic cells, 2/3 of the folate receptor pool is located in an internal (acid resistant) compartment, but phorbol 12-myristate 13-acetate (PMA) causes a shift such that 65-75% of the receptor pool resides on the surface of the plasma membrane. This new steady state is likely the result of an increased rate of receptor movement. In addition, PMA increases the rate of 5- methyl[3H]tetrahydrofolate delivery to the cytoplasm 1.8 fold. Using known inhibitors of potocytosis, we were able to show that the increased rate of delivery is receptor mediated. Comparison of the time courses of the PMA effects on folate receptor redistribution assessed by membrane binding of [3H]folic acid and 5-methyl[3H]tetrahydrofolate delivery to the cytoplasm suggests that PMA may be activating more than one protein kinase C independent signal transduction pathway. PMA is the first reported positive modulator of receptor mediated folate uptake.

Original languageEnglish (US)
Pages (from-to)157-169
Number of pages13
JournalBiochimica et Biophysica Acta - Molecular Cell Research
Volume1401
Issue number2
DOIs
StatePublished - Feb 4 1998

Keywords

  • Folate
  • Folate receptor
  • Phorbol 12-myristate 13-acetate
  • Potocytosis

ASJC Scopus subject areas

  • Molecular Biology
  • Cell Biology

Fingerprint Dive into the research topics of 'PMA alters folate receptor distribution in the plasma membrane and increases the rate of 5-methyltetrahydrofolate delivery in mature MA104 cells'. Together they form a unique fingerprint.

  • Cite this