scholarly journals Association of folate receptor (folr1, folr2, folr3) and reduced folate carrier (slc19a1) genes with meningomyelocele

2010 ◽  
Vol 88 (8) ◽  
pp. 689-694 ◽  
Author(s):  
Michelle R. O'Byrne ◽  
Kit Sing Au ◽  
Alanna C. Morrison ◽  
Jone-Ing Lin ◽  
Jack M. Fletcher ◽  
...  
Keyword(s):  
Folate Receptor ◽  
Reduced Folate Carrier

scholarly journals Upregulation of reduced folate carrier by vitamin D enhances brain folate uptake in mice lacking folate receptor alpha

2019 ◽  
Vol 116 (35) ◽  
pp. 17531-17540 ◽  
Author(s):  
Camille Alam ◽  
Susanne Aufreiter ◽  
Constantine J. Georgiou ◽  
Md. Tozammel Hoque ◽  
Richard H. Finnell ◽  
...  
Keyword(s):  
Vitamin D ◽  
Choroid Plexus ◽  
Folate Receptor ◽  
Functional Expression ◽  
Transport Systems ◽  
Reduced Folate Carrier ◽  
Folate Transport ◽  
Folate Receptor Alpha ◽  
Receptor Alpha ◽  
Neurometabolic Disorders

Folates are critical for central nervous system function. Folate transport is mediated by 3 major pathways, reduced folate carrier (RFC), proton-coupled folate transporter (PCFT), and folate receptor alpha (FRα/Folr1), known to be regulated by ligand-activated nuclear receptors. Cerebral folate delivery primarily occurs at the choroid plexus through FRα and PCFT; inactivation of these transport systems can result in very low folate levels in the cerebrospinal fluid causing childhood neurodegenerative disorders. These disorders have devastating effects in young children, and current therapeutic approaches are not sufficiently effective. Our group has previously reported in vitro that functional expression of RFC at the blood–brain barrier (BBB) and its upregulation by the vitamin D nuclear receptor (VDR) could provide an alternative route for brain folate uptake. In this study, we further demonstrated in vivo, using Folr1 knockout (KO) mice, that loss of FRα led to a substantial decrease of folate delivery to the brain and that pretreatment of Folr1 KO mice with the VDR activating ligand, calcitriol (1,25-dihydroxyvitamin D3), resulted in over a 6-fold increase in [13C5]-5-formyltetrahydrofolate ([13C5]-5-formylTHF) concentration in brain tissues, with levels comparable to wild-type animals. Brain-to-plasma concentration ratio of [13C5]-5-formylTHF was also significantly higher in calcitriol-treated Folr1 KO mice (15-fold), indicating a remarkable enhancement in brain folate delivery. These findings demonstrate that augmenting RFC functional expression at the BBB could effectively compensate for the loss of Folr1-mediated folate uptake at the choroid plexus, providing a therapeutic approach for neurometabolic disorders caused by defective brain folate transport.

scholarly journals Endocytosis of GPI-linked membrane folate receptor-alpha.

1996 ◽  
Vol 132 (1) ◽  
pp. 35-47 ◽  
Author(s):  
S Rijnboutt ◽  
G Jansen ◽  
G Posthuma ◽  
J B Hynes ◽  
J H Schornagel ◽  
...  
Keyword(s):  
Plasma Membrane ◽  
Folate Receptor ◽  
Large Fraction ◽  
Integral Membrane Protein ◽  
Endocytic Pathway ◽  
Reduced Folate Carrier ◽  
Membrane Domains ◽  
Chemotherapeutic Drugs ◽  
Folate Receptors ◽  
Triton X

GPI-linked membrane folate receptors (MFRs) have been implicated in the receptor-mediated uptake of reduced folate cofactors and folate-based chemotherapeutic drugs. We have studied the biosynthetic transport to and internalization of MFR isoform alpha in KB-cells. MFR-alpha was synthesized as a 32-kD protein and converted in a maturely glycosylated 36-38-kD protein 1 h after synthesis. 32-kD MFR-alpha was completely soluble in Triton X-100 at 0 degree C. In contrast, only 33% of the 36-38-kD species could be solubilized at these conditions whereas complete solubilization was obtained in Triton X-100 at 37 degrees C or in the presence of saponin at 0 degree C. Similar solubilization characteristics were found when MFR-alpha at the plasma membrane was labeled with a crosslinkable 125I-labeled photoaffinity-analog of folic acid as a ligand. Triton X-100-insoluble membrane domains containing MFR-alpha could be separated from soluble MFR-alpha on sucrose flotation gradients. Only Triton X-100 soluble MFR-alpha was internalized from the plasma membrane. The reduced-folate-carrier, an integral membrane protein capable of translocating (anti-)folates across membranes, was completely excluded from the Triton X-100-resistant membrane domains. Internalized MFR-alpha recycled slowly to the cell surface during which it remained soluble in Triton X-100 at 0 degree C. Using immunoelectron microscopy, we found MFR-alpha along the entire endocytic pathway: in clathrin-coated buds and vesicles, and in small and large endosomal vacuoles. In conclusion, our data indicate that a large fraction, if not all, of internalizing MFR-alpha bypasses caveolae.

scholarly journals Dynamics of antifolate transport via the reduced folate carrier and the membrane folate receptor in murine leukaemia cells in vitro and in vivo

2008 ◽  
Vol 62 (6) ◽  
pp. 937-948 ◽  
Author(s):  
Robert Mauritz ◽  
Godefridus J. Peters ◽  
Ietje Kathmann ◽  
Habte Teshale ◽  
Paul Noordhuis ◽  
...  
Keyword(s):  
Folate Receptor ◽  
Reduced Folate Carrier
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