All-In Breakdown

folate receptor

ScientificConcept

A protein that is essential for transporting folate (a B vitamin) into cells. The podcast discusses a theory where auto-antibodies against this receptor can lead to cellular dysfunction and contribute to the development of autism.

First Mentioned

9/27/2025, 5:10:03 AM

Last Updated

9/27/2025, 5:12:05 AM

Research Retrieved

9/27/2025, 5:12:05 AM

Summary

Folate receptors are crucial cell surface proteins responsible for binding folate and its reduced derivatives, such as tetrahydrofolate, and facilitating their transport into cells. Once internalized, these monoglutamate forms are converted into biologically active polyglutamate forms, like 5-methyltetrahydrofolate, which are essential cofactors in one-carbon metabolism. These receptors are typically anchored to the cell membrane via a GPI anchor. The family includes human proteins such as Folate Receptor 1 (FOLR1), also known as the adult folate receptor; Folate Receptor 2 (FOLR2), the fetal folate receptor; and Folate Receptor 3 (FOLR3), also referred to as folate receptor gamma. Beyond their metabolic role, folate receptors are also implicated in various physiological and pathological contexts, including their increased expression in certain malignant tumors. Notably, a scientific theory involving autoimmunity and the folate receptor has been discussed in relation to a potential link between autism and Tylenol (acetaminophen) use during pregnancy, highlighting their broader significance in health and disease.

Referenced in 1 Document
Research Data
Extracted Attributes
  • Function

    Binds folate and reduced folic acid derivatives, mediates delivery of tetrahydrofolate into cells

  • Regulation

    Expression increases when extracellular levels of folate are low

  • Role in cancer

    Folate receptor alpha (FRalpha) levels are high in specific malignant tumors of epithelial origin

  • Binding affinity

    Binds physiologic folates with nmol/L affinities

  • Biological activity

    Polyglutamate forms act as enzymatic cofactors in folate-dependent one-carbon metabolism

  • Human family member

    Folate Receptor 3 (FOLR3), also known as folate receptor gamma

  • Mechanism of action

    Converts monoglutamate forms to polyglutamate forms (e.g., 5-methyltetrahydrofolate) inside cells

  • Membrane attachment

    Attached to cell membrane by a GPI anchor

  • Related protein (chicken)

    Riboflavin-binding protein, required for riboflavin transport to developing oocyte

Wikipedia
View on Wikipedia
Folate receptor

Folate receptors bind folate and reduced folic acid derivatives and mediates delivery of tetrahydrofolate to the interior of cells. It is then converted from monoglutamate to polyglutamate forms - such as 5-methyltetrahydrofolate - as only monoglutamate forms can be transported across cell membranes. Polyglutamate forms are biologically active enzymatic cofactors required for many folate-dependent processes such as folate-dependent one-carbon metabolism. These proteins are attached to the membrane by a GPI anchor. A riboflavin-binding protein required for the transport of riboflavin to the developing oocyte in chicken also belong to this family. Human proteins from this family include: FOLR1: folate receptor 1 (adult), FOLR2: folate receptor 2 (fetal), and FOLR3: folate receptor gamma.

Web Search Results
  • Folate receptor function is regulated in response to different cellular ...

    The folate receptor (FR) binds physiologic folates with nmol/L affinities and is expected to play an important role in transporting serum folates into cells that express this receptor. Although it has been shown that FR expression increases when extracellular levels of folate are low, whether this receptor is regulated in response to altered cellular requirements for folates or by intracellular levels of this vitamin has not been investigated. In this study, FR levels, FR function and cellular [...] ### Add to Collections ### Add to My Bibliography ## Your saved search ## Create a file for external citation management software ## Your RSS Feed ### Actions ### Page navigation # Folate receptor function is regulated in response to different cellular growth rates in cultured mammalian cells ### Affiliation # Folate receptor function is regulated in response to different cellular growth rates in cultured mammalian cells ### Authors ### Affiliation ## Abstract [...] folate levels were measured in cells with different growth rates to investigate FR regulation of this receptor under conditions in which cellular requirements for folate are altered. These experiments used cells that endogenously express FR (JAR, Caco-2 and MA-104) and cells stably transfected with this receptor (FRGPI-16 and FRTM-8). FR function decreased as cellular growth slowed in four of the five cell lines examined. Although cellular folate levels also decreased as cells reached

  • The role of folate receptor alpha in cancer development ... - PubMed

    Folate receptor alpha (FRalpha) is a membrane-bound protein with high affinity for binding and transporting physiologic levels of folate into cells. Folate is a basic component of cell metabolism and DNA synthesis and repair, and rapidly dividing cancer cells have an increased requirement for folate to maintain DNA synthesis, an observation supported by the widespread use of antifolates in cancer chemotherapy. FRalpha levels are high in specific malignant tumors of epithelial origin compared to [...] ### Add to Collections ### Add to My Bibliography ## Your saved search ## Create a file for external citation management software ## Your RSS Feed ### Full text links Wiley full text link ### Actions ### Page navigation # The role of folate receptor alpha in cancer development, progression and treatment: cause, consequence or innocent bystander? ### Affiliation [...] National Library of Medicine 8600 Rockville Pike Bethesda, MD 20894 Web Policies FOIA HHS Vulnerability Disclosure Help Accessibility Careers

  • Folate receptor - Wikipedia

    Folate receptors bind folate and reduced folic acid derivatives and mediates delivery of tetrahydrofolate to the interior of cells.( It is then converted from monoglutamate to polyglutamate forms - such as 5-methyltetrahydrofolate - as only monoglutamate forms can be transported across cell membranes. Polyglutamate forms are biologically active enzymatic cofactors required for many folate-dependent processes such as folate-dependent one-carbon metabolism. These proteins are attached to the [...] Human proteins from this family include: FOLR1: folate receptor 1 (adult), FOLR2: folate receptor 2 (fetal), and FOLR3: folate receptor gamma. References [edit] [...] Download as PDF Printable version In other projects Wikidata item From Wikipedia, the free encyclopedia Protein family | Folate receptor family | | Identifiers | | Symbol | Folate_rec | | Pfam | PF03024 | | InterPro | IPR004269 | | | show Available protein structures: | | Pfam | structures / ECOD | | PDB | RCSB PDB; PDBe; PDBj | | PDBsum | structure summary | |

  • Folate receptors and transporters: biological role and diagnostic ...

    Article Google Scholar 13. Assaraf YG, Leamon CP, Reddy JA. The folate receptor as a rational therapeutic target for personalized cancer treatment. Drug Resist Updat. 2014;17:89–95. Article Google Scholar 14. Date SS, Fiori MC, Altenberg GA, Jansen M. Expression in Sf9 insect cells, purification and functional reconstitution of the human proton-coupled folate transporter (PCFT, SLC46A1). PLoS One. 2017;12:e0177572. [...] Article CAS Google Scholar 38. van der Heijden JW, Oerlemans R, Dijkmans B, Qi H, Laken C, Lems W, et al. Folate receptor beta as a potential delivery route for novel folate antagonists to macrophages in the synovial tissue of rheumatoid arthritis patients. Arthritis Rheum. 2009;60:12–21. [...] CAS PubMed Google Scholar 50. Ab O, Whiteman KR, Bartle LM, Sun X, Singh R, Tavares D, et al. IMGN853, a folate receptor-α (FRα)-targeting antibody-drug conjugate, exhibits potent targeted antitumor activity against FRα-expressing tumors. Mol Cancer Ther. 2015;14:1605–13.

  • Noncanonical function of folate through folate receptor 1 during ...

    receptor that elicits Ca2+ transients to change cytoskeletal dynamics55."),56."),57."). Nevertheless, the amoeba’s folate receptor is a G-protein coupled receptor, unlike in vertebrates where FOLR1 is a GPI-anchored protein. This poses the interesting consideration on whether folate receptor evolved from the self-contained signaling receptor to a form that needs to partner with other transmembrane and intracellular molecules to elicit signaling. A non-metabolic function for folate through FOLR1 [...] Article CAS PubMed Google Scholar 16. Balashova, O. A., Visina, O. & Borodinsky, L. N. Folate receptor 1 is necessary for neural plate cell apical constriction during Xenopus neural tube formation. Development 144, 1518–1530 (2017). CAS PubMed PubMed Central Google Scholar 17. Piedrahita, J. A. et al. Mice lacking the folic acid-binding protein Folbp1 are defective in early embryonic development. Nat. Genet. 23, 228–232 (1999). [...] Article CAS PubMed Google Scholar 9. Alam, C. et al. Upregulation of reduced folate carrier by vitamin D enhances brain folate uptake in mice lacking folate receptor alpha. Proc. Natl Acad. Sci. USA 116, 17531–17540 (2019). Article ADS CAS PubMed PubMed Central Google Scholar 10. Nawaz, F. Z. & Kipreos, E. T. Emerging roles for folate receptor FOLR1 in signaling and cancer. Trends Endocrinol. Metab. 33, 159–174 (2022).