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

Item Type:

Preprint

Title:

Creators Name:

Kowalczyk, I. and Lee, C. and Schuster, E. and Hoeren, J. and Trivigno, V. and Riedel, L. and Goerne, J. and Wallingford, J.B. and Hammes-Lewin, A. and Feistel, K.

Abstract:

Recent studies have revealed that 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 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 (LOF) 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 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 laevis

Source:

bioRxiv

Publisher:

Cold Spring Harbor Laboratory Press

Article Number:

2020.07.15.205252

Date:

16 July 2020

Official Publication:

https://doi.org/10.1101/2020.07.15.205252

Related to:

URL	URL Type
https://edoc.mdc-berlin.de/19921/	Final version

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