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

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 to elucidate the etiology of Lrp2-related N...

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Veröffentlicht in:Development (Cambridge) 2021-01, Vol.148 (2)
Hauptverfasser: Kowalczyk, Izabela, Lee, Chanjae, Schuster, Elisabeth, Hoeren, Josefine, Trivigno, Valentina, Riedel, Levin, Görne, Jessica, Wallingford, John B, Hammes, Annette, Feistel, Kerstin
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container_issue 2
container_start_page
container_title Development (Cambridge)
container_volume 148
creator Kowalczyk, Izabela
Lee, Chanjae
Schuster, Elisabeth
Hoeren, Josefine
Trivigno, Valentina
Riedel, Levin
Görne, Jessica
Wallingford, John B
Hammes, Annette
Feistel, Kerstin
description 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 to elucidate the etiology of Lrp2-related NTDs. 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.
doi_str_mv 10.1242/dev.195008
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subjects Animals
Cell Membrane - metabolism
Cell Polarity
Endocytosis
Intracellular Space - metabolism
Low Density Lipoprotein Receptor-Related Protein-2 - deficiency
Low Density Lipoprotein Receptor-Related Protein-2 - metabolism
Mice
Mice, Inbred C57BL
Models, Biological
Morphogenesis
Neural Tube - embryology
Neural Tube - metabolism
Neural Tube - ultrastructure
Neuroepithelial Cells - metabolism
Prosencephalon - metabolism
Protein Binding
Xenopus
Xenopus Proteins - metabolism
title Neural tube closure requires the endocytic receptor Lrp2 and its functional interaction with intracellular scaffolds
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