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Characterization of folate uptake by choroid plexus epithelial cells in a rat primary culture model
Authors:Wollack Jan B  Makori Benedette  Ahlawat Stuti  Koneru Rajeth  Picinich Sonia C  Smith Angela  Goldman I David  Qiu Andong  Cole Peter D  Glod John  Kamen Barton
Institution:Department of Pediatrics, Cancer Institute of New Jersey, Robert Wood Johnson Medical School, New Brunswick, New Jersey, USA;
Department of Pharmacology, Graduate School of Biomedical Sciences, University of Medicine and Dentistry of New Jersey, Piscataway, New Jersey, USA;
Departments of Medicine and Molecular Pharmacology, Albert Einstein College of Medicine, New York, USA
Abstract:Reduced derivatives of folic acid (folates) play a critical role in the development, function and repair of the CNS. However, the molecular systems regulating folate uptake and homeostasis in the central nervous system remain incompletely defined. Choroid plexus epithelial cells express high levels of folate receptor α (FRα) suggesting that the choroid plays an important role in CNS folate trafficking and maintenance of CSF folate levels. We have characterized 5-methyltetrahydrofolate (5-MTHF) uptake and metabolism by primary rat choroid plexus epithelial cells in vitro . Two distinct processes are apparent; one that is FRα dependent and one that is independent of the receptor. FRα binds 5-MTHF with high affinity and facilitates efficient uptake of 5-MTHF at low extracellular folate concentrations; a lower affinity FRα independent system accounts for increased folate uptake at higher concentrations. Cellular metabolism of 5-MTHF depends on the route of folate entry into the cell. 5-MTHF taken up via a non-FRα -mediated process is rapidly metabolized to folylpolyglutamates, whereas 5-MTHF that accumulates via FRα remains non-metabolized, supporting the hypothesis that FRα may be part of a pathway for transcellular movement of the vitamin. The proton-coupled folate transporter, proton-coupled folate transporter (PCFT), mRNA was also shown to be expressed in choroid plexus epithelial cells. This is consistent with the role we have proposed for proton-coupled folate transporter in FRα-mediated transport as the mechanism of export of folates from the endocytic compartment containing FRα.
Keywords:5-methyltetrahydrofolate  choroid plexus  folate receptor  proton-coupled folate transporter  reduced folate carrier
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