A role for the proton-coupled folate transporter (PCFT-SLC46A1) in folate receptor-mediated endocytosis

Rongbao Zhao, Sang Hee Min, Yanhua Wang, Estela Campanella, Philip S. Low, I. David Goldman

Research output: Contribution to journalArticle

94 Scopus citations

Abstract

Recently, this laboratory identified a proton-coupled folate transporter (PCFT), with optimal activity at low pH. PCFT is critical to intestinal folate absorption and transport into the central nervous system because there are loss-of-function mutations in this gene in the autosomal recessive disorder, hereditary folate malabsorption. The current study addresses the role PCFT might play in another transport pathway, folate receptor (FR)-mediated endocytosis. FRα cDNA was transfected into novel PCFT+ and PCFT- HeLa sublines. FRα was shown to bind and trap folates in vesicles but with minimal export into the cytosol in PCFT- cells. Cotransfection of FRα and PCFT resulted in enhanced folate transport into cytosol as compared with transfection of FRα alone. Probenecid did not inhibit folate binding to FR, but inhibited PCFT-mediated transport at endosomal pH, and blocked FRα- mediated transport into the cytosol. FRα and PCFT co-localized to the endosomal compartment. These observations (i) indicate that PCFT plays a role in FRα-mediated endocytosis by serving as a route of export of folates from acidified endosomes and (ii) provide a functional role for PCFT in tissues in which it is expressed, such as the choroid plexus, where the extracellular milieu is at neutral pH.

Original languageEnglish (US)
Pages (from-to)4267-4274
Number of pages8
JournalJournal of Biological Chemistry
Volume284
Issue number7
DOIs
StatePublished - Feb 13 2009

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology

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