title: Identification of an intestinal folate transporter and the molecular basis for hereditary folate malabsorption.
abstract: Folates are essential nutrients that are required for one-carbon biosynthetic and epigenetic processes. While folates are absorbed in the acidic milieu of the upper small intestine, the underlying absorption mechanism has not been defined. We now report the identification of a human proton-coupled, high-affinity folate transporter that recapitulates properties of folate transport and absorption in intestine and in various cell types at low pH. We demonstrate that a loss-of-function mutation in this gene is the molecular basis for hereditary folate malabsorption in a family with this disease. This transporter was previously reported to be a lower-affinity, pH-independent heme carrier protein, HCP1. However, the current study establishes that a major function of this gene product is proton-coupled folate transport required for folate homeostasis in man, and we have thus amended the name to PCFT/HCP1.
authors.affiliation: Department of Medicine, Albert Einstein College of Medicine, 1300 Morris Park Avenue, Bronx, NY 10461, USA.
authors.forename: Andong
authors.initials: A
authors.lastname: Qiu
authors.forename: Michaela
authors.initials: M
authors.lastname: Jansen
authors.forename: Antoinette
authors.initials: A
authors.lastname: Sakaris
authors.forename: Sang Hee
authors.initials: SH
authors.lastname: Min
authors.forename: Shrikanta
authors.initials: S
authors.lastname: Chattopadhyay
authors.forename: Eugenia
authors.initials: E
authors.lastname: Tsai
authors.forename: Claudio
authors.initials: C
authors.lastname: Sandoval
authors.forename: Rongbao
authors.initials: R
authors.lastname: Zhao
authors.forename: Myles H
authors.initials: MH
authors.lastname: Akabas
authors.forename: I David
authors.initials: ID
authors.lastname: Goldman
mesh_terms: D000818:Animals; D001692:Biological Transport; D018938:Caco-2 Cells; D045744:Cell Line, Tumor; D004594:Electrophysiology; D005492:Folic Acid / Q000737:chemistry / Q000378:metabolism*; D005786:Gene Expression Regulation; D006367:HeLa Cells; D006801:Humans; D006863:Hydrogen-Ion Concentration; D007413:Intestinal Mucosa / Q000378:metabolism*; D007700:Kinetics; D008286:Malabsorption Syndromes / Q000235:genetics*; D026901:Membrane Transport Proteins / Q000235:genetics / Q000378:metabolism*; D009865:Oocytes; D010375:Pedigree; D058979:Proton-Coupled Folate Transporter; D034622:RNA Interference; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D013379:Substrate Specificity; D014981:Xenopus
chemical_list: D026901:Membrane Transport Proteins; D058979:Proton-Coupled Folate Transporter; D012333:RNA, Messenger; C505058:SLC46A1 protein, human; D005492:Folic Acid