Noncanonical function of folate through folate receptor 1 during neural tube formation
Abstract Folate supplementation reduces the occurrence of neural tube defects (NTDs), birth defects consisting in the failure of the neural tube to form and close. The mechanisms underlying NTDs and their prevention by folate remain unclear. Here we show that folate receptor 1 (FOLR1) is necessary f...
| Main Authors: | , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Nature Portfolio
2024-02-01
|
| Series: | Nature Communications |
| Online Access: | https://doi.org/10.1038/s41467-024-45775-1 |
| _version_ | 1797274137990791168 |
|---|---|
| author | Olga A. Balashova Alexios A. Panoutsopoulos Olesya Visina Jacob Selhub Paul S. Knoepfler Laura N. Borodinsky |
| author_facet | Olga A. Balashova Alexios A. Panoutsopoulos Olesya Visina Jacob Selhub Paul S. Knoepfler Laura N. Borodinsky |
| author_sort | Olga A. Balashova |
| collection | DOAJ |
| description | Abstract Folate supplementation reduces the occurrence of neural tube defects (NTDs), birth defects consisting in the failure of the neural tube to form and close. The mechanisms underlying NTDs and their prevention by folate remain unclear. Here we show that folate receptor 1 (FOLR1) is necessary for the formation of neural tube-like structures in human-cell derived neural organoids. FOLR1 knockdown in neural organoids and in Xenopus laevis embryos leads to NTDs that are rescued by pteroate, a folate precursor that is unable to participate in metabolism. We demonstrate that FOLR1 interacts with and opposes the function of CD2-associated protein, molecule essential for apical endocytosis and turnover of C-cadherin in neural plate cells. In addition, folates increase Ca2+ transient frequency, suggesting that folate and FOLR1 signal intracellularly to regulate neural plate folding. This study identifies a mechanism of action of folate distinct from its vitamin function during neural tube formation. |
| first_indexed | 2024-03-07T14:55:03Z |
| format | Article |
| id | doaj.art-f923a482aa8247899a9dcf1a160c9ade |
| institution | Directory Open Access Journal |
| issn | 2041-1723 |
| language | English |
| last_indexed | 2024-03-07T14:55:03Z |
| publishDate | 2024-02-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Nature Communications |
| spelling | doaj.art-f923a482aa8247899a9dcf1a160c9ade2024-03-05T19:31:40ZengNature PortfolioNature Communications2041-17232024-02-0115111710.1038/s41467-024-45775-1Noncanonical function of folate through folate receptor 1 during neural tube formationOlga A. Balashova0Alexios A. Panoutsopoulos1Olesya Visina2Jacob Selhub3Paul S. Knoepfler4Laura N. Borodinsky5Department of Physiology & Membrane Biology, Shriners Hospitals for Children Northern California, University of California Davis, School of MedicineDepartment of Physiology & Membrane Biology, Shriners Hospitals for Children Northern California, University of California Davis, School of MedicineDepartment of Physiology & Membrane Biology, Shriners Hospitals for Children Northern California, University of California Davis, School of MedicineTufts–USDA Human Nutrition Research Center on AgingDepartment of Cell Biology & Human Anatomy, Shriners Hospitals for Children Northern California, University of California Davis, School of MedicineDepartment of Physiology & Membrane Biology, Shriners Hospitals for Children Northern California, University of California Davis, School of MedicineAbstract Folate supplementation reduces the occurrence of neural tube defects (NTDs), birth defects consisting in the failure of the neural tube to form and close. The mechanisms underlying NTDs and their prevention by folate remain unclear. Here we show that folate receptor 1 (FOLR1) is necessary for the formation of neural tube-like structures in human-cell derived neural organoids. FOLR1 knockdown in neural organoids and in Xenopus laevis embryos leads to NTDs that are rescued by pteroate, a folate precursor that is unable to participate in metabolism. We demonstrate that FOLR1 interacts with and opposes the function of CD2-associated protein, molecule essential for apical endocytosis and turnover of C-cadherin in neural plate cells. In addition, folates increase Ca2+ transient frequency, suggesting that folate and FOLR1 signal intracellularly to regulate neural plate folding. This study identifies a mechanism of action of folate distinct from its vitamin function during neural tube formation.https://doi.org/10.1038/s41467-024-45775-1 |
| spellingShingle | Olga A. Balashova Alexios A. Panoutsopoulos Olesya Visina Jacob Selhub Paul S. Knoepfler Laura N. Borodinsky Noncanonical function of folate through folate receptor 1 during neural tube formation Nature Communications |
| title | Noncanonical function of folate through folate receptor 1 during neural tube formation |
| title_full | Noncanonical function of folate through folate receptor 1 during neural tube formation |
| title_fullStr | Noncanonical function of folate through folate receptor 1 during neural tube formation |
| title_full_unstemmed | Noncanonical function of folate through folate receptor 1 during neural tube formation |
| title_short | Noncanonical function of folate through folate receptor 1 during neural tube formation |
| title_sort | noncanonical function of folate through folate receptor 1 during neural tube formation |
| url | https://doi.org/10.1038/s41467-024-45775-1 |
| work_keys_str_mv | AT olgaabalashova noncanonicalfunctionoffolatethroughfolatereceptor1duringneuraltubeformation AT alexiosapanoutsopoulos noncanonicalfunctionoffolatethroughfolatereceptor1duringneuraltubeformation AT olesyavisina noncanonicalfunctionoffolatethroughfolatereceptor1duringneuraltubeformation AT jacobselhub noncanonicalfunctionoffolatethroughfolatereceptor1duringneuraltubeformation AT paulsknoepfler noncanonicalfunctionoffolatethroughfolatereceptor1duringneuraltubeformation AT lauranborodinsky noncanonicalfunctionoffolatethroughfolatereceptor1duringneuraltubeformation |