Key Words: Regulation,structure/function, physiological and pharmacological roles of a proton-coupled folate transporter and the genetics of hereditary folate malabsorption
The Goldman laboratory cloned the proton-coupled folate transporter (PCFT) that is responsible for (i) the intestinal absorption of folates, (ii) transport of folates across the choroid plexus barrier, and (iii) transport of antifolates into cancer cells within the acidic microenvironment in which they grow (Cell 127:917-28, '06). Ongoing studies are exploring the structure/function of this transporter within the context of an evolving molecular model. A particular focus is on the elements that play a crucial role in folate substrate and proton binding, proton coupling, and are determinant of the conformational states of the carrier. Loss-of-function PCFT mutations are the molecular basis for the autosomal recessive disorder, hereditary folate malabsorption, and this laboratory is a focal point for the study of the functional consequences of mutations detected in PCFT in patients with HFM world-wide.
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