Folate receptor, or folate-binding protein (FBP), has a high affinity for folic acid and for several reduced folic acid derivatives and mediates delivery of 5-methyltetrahydrofolate to the interior of cells. Membrane-bound and soluble forms of a high-affinity folate binding protein have been found in kidney, placenta, serum, milk, and in several cell lines. The 2 forms have similar binding characteristics for folates, are immunologically crossreactive, and, based upon limited amino acid sequence data, are nearly identical. There may be a precursor-product relationship between the membrane and soluble forms, the membrane form having additional amino acid residues and greater molecular weight. The membrane form has been shown to mediate the transport of folate in cells grown in physiologic concentrations of folate.
NCBI Summary:
The protein encoded by this gene is a member of the folate receptor family. Members of this gene family bind folic acid and its reduced derivatives, and transport 5-methyltetrahydrofolate into cells. This gene product is a secreted protein that either anchors to membranes via a glycosyl-phosphatidylinositol linkage or exists in a soluble form. Mutations in this gene have been associated with neurodegeneration due to cerebral folate transport deficiency. Due to the presence of two promoters, multiple transcription start sites, and alternative splicing, multiple transcript variants encoding the same protein have been found for this gene. [provided by RefSeq, Oct 2009]
General function
Receptor
Comment
Cellular localization
Cytoplasmic, Plasma membrane
Comment
Ovarian function
Early embryo development
Comment
Maternally Contributed Folate Receptor 1 Is Expressed in Ovarian Follicles and Contributes to Preimplantation Development. Strandgaard T et al. (2017) Folates have been shown to play a crucial role for proper development of the embryo as folate deficiency has been associated with reduced developmental capacity such as increased risk of fetal neural tube defects and spontanous abortion. Transcripts encoding the reduced folate carrier RFC1 (SLC19A1 protein) and the high-affinity folate receptor FOLR1 are expressed in oocytes and preimplantation embryos, respectively. In this study, we observed maternally contributed FOLR1 protein during mouse and human ovarian follicle development, and 2-cell mouse embryos. In mice, FOLR1 was highly enriched in oocytes from primary, secondary and tertiary follicles, and in the surrounding granulosa cells. Interestingly, during human follicle development, we noted a high and specific presence of FOLR1 in oocytes from primary and intermediate follicles, but not in the granulosa cells. The distribution of FOLR1 in follicles was noted as membrane-enriched but also seen in the cytoplasm in oocytes and granulosa cells. In 2-cell embryos, FOLR1-eGFP fusion protein was detected as cytoplasmic and membrane-associated dense structures, resembling the distribution pattern observed in ovarian follicle development. Knock-down of Folr1 mRNA function was accomplished by microinjection of short interference (si)RNA targeting Folr1, into mouse pronuclear zygotes. This revealed a reduced capacity of Folr1 siRNA-treated embryos to develop to blastocyst compared to the siRNA-scrambled control group, indicating that maternally contributed protein and zygotic transcripts sustain embryonic development combined. In summary, maternally contributed FOLR1 protein appears to maintain ovarian functions, and contribute to preimplantation development combined with embryonically synthesized FOLR1.//////////////////
Expression regulated by
Comment
Ovarian localization
Oocyte, Granulosa
Comment
The dormant and the fully competent oocyte: comparing the transcriptome of human oocytes from primordial follicles and in metaphase ii. Grndahl ML et al. Oocytes become enclosed in primordial follicles during fetal life and remain there dormant until activation followed by growth and meiotic resumption. Current knowledge about the molecular pathways involved in oogenesis is incomplete. This study identifies the specific transcriptome of the human oocyte in the quiescent state and at the pinnacle of maturity at ovulation. In silico bioinformatic comparisons were performed between transcriptome of human oocytes from dormant primordial follicles and that of human metaphase II (MII) oocytes and granulosa cells and unique gene expression profiles were identified as well as functional and pathway enrichments associated with the oocytes from the two developmental hallmarks. A total of 729 genes were highly enriched in oocytes from primodial folllicles and 1456 genes were highly enriched in MII oocytes (>10 fold, p<0.001) representing functional categories such as cell cycle regulation, DNA protection and epigenetics, with representative genes validated by qPCR analysis. Dominating canonical pathways in the oocytes from primordial follicles were androgen, estrogen receptor, glucocortocoid receptor and PI3 K/AKT signaling (p<0.001). In the MII, mitotic roles of polo-like kinases, estrogen receptor, JAK/Stat signaling (p<0.001) and the ERK/MAPK (p<0.01) signaling were enriched. Some of the highly differentially expressed genes were completely new in human reproduction (CDR1, TLC1A, UHRF2) while other genes (ABO, FOLR1 (folate receptor), CHRNA3 (nicotine receptor)) may relate to clinical observations as diverse as premature ovarian failure, folic acid deficiency and smoking affecting female fertility. The in silico analysis identified novel reproduction associated genes and highlighted molecular mechanisms and pathways associated to the unique functions of the human oocyte in its two extremes of the folliculogenesis. The data provides a fundamental basis for future functional studies in regulation of human oogenesis.
Campbell IG, et al describe the isolation of a complementary DNA (cDNA) sequence encoding the ovarian cancer-associated antigen recognized by monoclonal antibody MOv18 and its identification as a high-affinity folate-binding protein (FBP). Functional cDNA clones were isolated using mRNA from the ovarian carcinoma cell line SKOV3 and colon carcinoma cell line HT29, by transient expression in WOP cells and selection of expressing cells by adhesion to antibody-coated magnetic beads. The cDNAs differed in the lengths of 5'- and 3'-noncoding regions, but they encoded identical peptides. A database search clearly showed them to be adult high-affinity FBPs with amino acid sequences identical with those isolated from normal placenta and several carcinoma cell lines. Reactivity of cell lines with MOv18 was quantitatively consistent with the expression of FBP mRNA. Southern hybridizations show evidence of a family of related genes and/or pseudogenes and were mapped to chromosome 11q13.3-14.1 by fluorescent in situ hybridization using cosmid clones containing part of this region. Also identified were two PstI polymorphisms of four and three alleles, respectively, and a two-allele MspI polymorphism. The folate-binding protein locus was not amplified in any of the 16 carcinoma cell lines tested and in only 1 of 10 serous adenocarcinomas, indicating that overexpression of FBP in ovarian cancer cannot, in general, be due to gene amplification.