Sign up to save your podcasts
Or
Share Neural tube closure requires the endocytic receptor Lrp2 and its functional interaction with intracellular scaffolds
Share to email
Share to Facebook
Share to X
Share to email
Share to Facebook
Share to X
Or
Neural tube closure requires the endocytic receptor Lrp2 and its functional interaction with intracellular scaffolds
Link to bioRxiv paper:
http://biorxiv.org/cgi/content/short/2020.07.15.205252v1?rss=1
Authors: Kowalczyk, I., Lee, C., Schuster, E., Hoeren, J., Trivigno, V., Riedel, L., Goerne, J., Wallingford, J. B., Hammes-Lewin, A., 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.
Summary statementAnalysis of neurulation in mouse and Xenopus reveals novel roles for Lrp2-mediated endocytosis in orchestrating apical constriction and planar cell polarity essential for neural tube closure.
Copy rights belong to original authors. Visit the link for more info
View all episodes
Link to bioRxiv paper:
http://biorxiv.org/cgi/content/short/2020.07.15.205252v1?rss=1
Authors: Kowalczyk, I., Lee, C., Schuster, E., Hoeren, J., Trivigno, V., Riedel, L., Goerne, J., Wallingford, J. B., Hammes-Lewin, A., 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.
Summary statementAnalysis of neurulation in mouse and Xenopus reveals novel roles for Lrp2-mediated endocytosis in orchestrating apical constriction and planar cell polarity essential for neural tube closure.
Copy rights belong to original authors. Visit the link for more info