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Neural tube closure requires the endocytic receptor Lrp2 and its functional interaction with intracellular scaffolds

Item Type:Article
Title:Neural tube closure requires the endocytic receptor Lrp2 and its functional interaction with intracellular scaffolds
Creators Name:Kowalczyk, I. and Lee, C. and Schuster, E. and Hoeren, J. and Trivigno, V. and Riedel, L. and Görne, J. and Wallingford, J.B. and Hammes, A. and Feistel, K.
Abstract:Pathogenic mutations in the endocytic receptor LRP2 in humans are associated with severe neural tube closure defects (NTDs) such as anencephaly and spina bifida. Here, we have combined analysis of neural tube closure in mouse and in the African Clawed Frog Xenopus laevis to elucidate the etiology of Lrp2-related NTDs. Lrp2 loss of function impaired neuroepithelial morphogenesis, culminating in NTDs that impeded anterior neural plate folding and neural tube closure in both model organisms. Loss of Lrp2 severely affected apical constriction as well as proper localization of the core planar cell polarity (PCP) protein Vangl2, demonstrating a highly conserved role of the receptor in these processes, which are essential for neural tube formation. In addition, we identified a novel functional interaction of Lrp2 with the intracellular adaptor proteins Shroom3 and Gipc1 in the developing forebrain. Our data suggest that, during neurulation, motifs within the intracellular domain of Lrp2 function as a hub that orchestrates endocytic membrane removal for efficient apical constriction, as well as PCP component trafficking in a temporospatial manner.
Keywords:Lrp2, Gipc1, Vangl2, Neural Tube Closure, Animals, Mice, Xenopus
Source:Development
ISSN:0950-1991
Publisher:Company of Biologists
Volume:148
Number:2
Page Range:dev195008
Date:26 January 2021
Official Publication:https://doi.org/10.1242/dev.195008
PubMed:View item in PubMed
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URLURL Type
https://edoc.mdc-berlin.de/19131/Preprint version

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