Identification of an intestinal folate transporter and the molecular basis for hereditary folate malabsorption

Authors:
Qiu A, Jansen M, Sakaris A, Min SH, Chattopadhyay S, Tsai E, Sandoval C, Zhao R, Akabas MH, Goldman ID
In:
Source: Cell
Publication Date: (2006)
Issue: 127(5): 917-28
Research Area:
Cancer Research/Cell Biology
Cells used in publication:
Caco-2
Species: human
Tissue Origin: colon
Platform:
Nucleofector® I/II/2b
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.