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J Cell Sci. 2014 May 15;127(Pt 10):2261-8. doi: 10.1242/jcs.140145. Epub 2014 Mar 17.

LRP2 mediates folate uptake in the developing neural tube.

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Max Delbrück Center for Molecular Medicine (MDC), Robert Rössle Strasse 10, 13125 Berlin, Germany.
Department of Nutritional Sciences, Dell Pediatric Research Institute, The University of Texas at Austin, Austin, TX 78723, USA.
Max Delbrück Center for Molecular Medicine (MDC), Robert Rössle Strasse 10, 13125 Berlin, Germany


The low-density lipoprotein (LDL) receptor-related protein 2 (LRP2) is a multifunctional cell-surface receptor expressed in the embryonic neuroepithelium. Loss of LRP2 in the developing murine central nervous system (CNS) causes impaired closure of the rostral neural tube at embryonic stage (E) 9.0. Similar neural tube defects (NTDs) have previously been attributed to impaired folate metabolism in mice. We therefore asked whether LRP2 might be required for the delivery of folate to neuroepithelial cells during neurulation. Uptake assays in whole-embryo cultures showed that LRP2-deficient neuroepithelial cells are unable to mediate the uptake of folate bound to soluble folate receptor 1 (sFOLR1). Consequently, folate concentrations are significantly reduced in Lrp2(-/-) embryos compared with control littermates. Moreover, the folic-acid-dependent gene Alx3 is significantly downregulated in Lrp2 mutants. In conclusion, we show that LRP2 is essential for cellular folate uptake in the developing neural tube, a crucial step for proper neural tube closure.


Embryonic development; Endocytic receptor; Folate; Folate receptor; LRP2; Neural tube closure defects

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