Abstract
This review surveys soluble Folate Receptors (FOLRs) in humans. FOLR1 and FOLR2 are equipped with cellular glycosylphosphatidylinositol (GPI) anchors. FOLR1 is secreted from epithelia with or without a micelle-encapsulated GPI-anchor into milk and other body fluids/secretions, e.g. semen where its interaction with spermatozoa indicates a role in male fertility. FOLR1 and FOLR2 serve as serum biomarkers of various diseases. FOLR3 possesses no GPI-anchor and originates from secretory granules of neutrophil granulocytes; its concentration in serum correlates to the FOLR3 content in leukocytes and rises with increased leukocyte counts (infection, malignancy and pregnancy). FOLR3 exerts anti-microbial and anti-tumor effects by depriving bacteria and tumor cells of natural folates. Megalin receptors mediate reabsorption of ultrafiltered folate-bound FOLR into cells of proximal kidney tubules and of folate-bound FOLR uptake in growing embryos. Megalin receptors overexpressed in malignant tumors could be suitable therapeutic targets for folate-conjugated cytotoxic agents utilizing soluble FOLRs as vectors.
| Original language | English |
|---|---|
| Article number | 140466 |
| Journal | Biochimica et biophysica acta. Proteins and proteomics |
| Volume | 1868 |
| Issue number | 10 |
| Pages (from-to) | 140466 |
| ISSN | 1570-9639 |
| DOIs | |
| Publication status | Published - Oct 2020 |
Keywords
- FOLR1 and FOLR2 as disease biomarkers
- FOLR2
- FOLR3 antimicrobial /antitumor effects
- FOLR3)
- Megalin receptors take up soluble FOLRs
- Neutrophil granulocytes secrete FOLR3 into plasma
- Soluble folate receptors (FOLR1
- Body Fluids/metabolism
- Neoplasms/etiology
- Disease Susceptibility
- Humans
- Folic Acid/metabolism
- Immunity, Innate
- Infections/etiology
- Host-Pathogen Interactions
- Animals
- Biomarkers
- Folate Receptor 1/blood
- Protein Binding
- Folate Receptor 2/blood
- Granulocytes/immunology
- Milk