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LRP2 mediates folate uptake in the developing neural tube

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Item Type:Article
Title:LRP2 mediates folate uptake in the developing neural tube
Creators Name:Kur, E. and Mecklenburg, N. and Cabrera, R.M. and Willnow, T.E. and Hammes, A.
Abstract: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 delivery of folate to neuroepithelial cells during neurulation. Uptake assays in whole embryo cultures showed that LRP2 deficient neuroepithelial cells are unable to mediate uptake of folate bound to soluble folate receptor 1 (sFOLR1). Consequently, folate concentrations are significantly reduced in Lrp2(-/-) embryos compared to control littermates. Moreover, the folic acid dependent gene Alx3 is significantly down regulated 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.
Keywords:LRP2, Embryonic Development, Endocytic Receptor, Folate, Folate Receptor, Neural Tube Closure Defects, Animals, Mice
Source:Journal of Cell Science
Publisher:Company of Biologists
Number:Pt 10
Page Range:2261-2268
Date:15 May 2014
Official Publication:https://doi.org/10.1242/jcs.140145
PubMed:View item in PubMed

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