Characterization of folate uptake by choroid plexus epithelial cells in a rat primary culture model

Jan B. Wollack, Benedette Makori, Stuti Ahlawat, Rajeth Koneru, Sonia C. Picinich, Angela Smith, I. David Goldman, Andong Qiu, Peter D. Cole, John Glod, Barton Kamen

Research output: Contribution to journalArticle

51 Citations (Scopus)

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.

Original languageEnglish (US)
Pages (from-to)1494-1503
Number of pages10
JournalJournal of Neurochemistry
Volume104
Issue number6
DOIs
StatePublished - Mar 2008

Fingerprint

Choroid Plexus
Folic Acid
Rats
Epithelial Cells
Proton-Coupled Folate Transporter
Metabolism
Transcytosis
Choroid
Neurology

Keywords

  • 5-methyltetrahydrofolate
  • Choroid plexus
  • Folate receptor
  • Proton-coupled folate transporter
  • Reduced folate carrier

ASJC Scopus subject areas

  • Biochemistry
  • Cellular and Molecular Neuroscience

Cite this

Wollack, J. B., Makori, B., Ahlawat, S., Koneru, R., Picinich, S. C., Smith, A., ... Kamen, B. (2008). Characterization of folate uptake by choroid plexus epithelial cells in a rat primary culture model. Journal of Neurochemistry, 104(6), 1494-1503. https://doi.org/10.1111/j.1471-4159.2007.05095.x

Characterization of folate uptake by choroid plexus epithelial cells in a rat primary culture model. / 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.

In: Journal of Neurochemistry, Vol. 104, No. 6, 03.2008, p. 1494-1503.

Research output: Contribution to journalArticle

Wollack, JB, Makori, B, Ahlawat, S, Koneru, R, Picinich, SC, Smith, A, Goldman, ID, Qiu, A, Cole, PD, Glod, J & Kamen, B 2008, 'Characterization of folate uptake by choroid plexus epithelial cells in a rat primary culture model', Journal of Neurochemistry, vol. 104, no. 6, pp. 1494-1503. https://doi.org/10.1111/j.1471-4159.2007.05095.x
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. / Characterization of folate uptake by choroid plexus epithelial cells in a rat primary culture model. In: Journal of Neurochemistry. 2008 ; Vol. 104, No. 6. pp. 1494-1503.
@article{fbfe62b426c04e489061a8df8b0c5916,
title = "Characterization of folate uptake by choroid plexus epithelial cells in a rat primary culture model",
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",
author = "Wollack, {Jan B.} and Benedette Makori and Stuti Ahlawat and Rajeth Koneru and Picinich, {Sonia C.} and Angela Smith and Goldman, {I. David} and Andong Qiu and Cole, {Peter D.} and John Glod and Barton Kamen",
year = "2008",
month = "3",
doi = "10.1111/j.1471-4159.2007.05095.x",
language = "English (US)",
volume = "104",
pages = "1494--1503",
journal = "Journal of Neurochemistry",
issn = "0022-3042",
publisher = "Wiley-Blackwell",
number = "6",

}

TY - JOUR

T1 - Characterization of folate uptake by choroid plexus epithelial cells in a rat primary culture model

AU - Wollack, Jan B.

AU - Makori, Benedette

AU - Ahlawat, Stuti

AU - Koneru, Rajeth

AU - Picinich, Sonia C.

AU - Smith, Angela

AU - Goldman, I. David

AU - Qiu, Andong

AU - Cole, Peter D.

AU - Glod, John

AU - Kamen, Barton

PY - 2008/3

Y1 - 2008/3

N2 - 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.

AB - 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.

KW - 5-methyltetrahydrofolate

KW - Choroid plexus

KW - Folate receptor

KW - Proton-coupled folate transporter

KW - Reduced folate carrier

UR - http://www.scopus.com/inward/record.url?scp=39849101600&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=39849101600&partnerID=8YFLogxK

U2 - 10.1111/j.1471-4159.2007.05095.x

DO - 10.1111/j.1471-4159.2007.05095.x

M3 - Article

C2 - 18086128

AN - SCOPUS:39849101600

VL - 104

SP - 1494

EP - 1503

JO - Journal of Neurochemistry

JF - Journal of Neurochemistry

SN - 0022-3042

IS - 6

ER -