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) |
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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 |
format | Article |
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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.</description><identifier>ISSN: 0950-1991</identifier><identifier>EISSN: 1477-9129</identifier><identifier>DOI: 10.1242/dev.195008</identifier><identifier>PMID: 33500317</identifier><language>eng</language><publisher>England: The Company of Biologists Ltd</publisher><subject>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</subject><ispartof>Development (Cambridge), 2021-01, Vol.148 (2)</ispartof><rights>2021. Published by The Company of Biologists Ltd.</rights><rights>2021. Published by The Company of Biologists Ltd 2021</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c378t-5a5c61f5e20c25b5c5914f8eb9ae23121eed1e5cc70524d65f789b166c1df1b43</citedby><cites>FETCH-LOGICAL-c378t-5a5c61f5e20c25b5c5914f8eb9ae23121eed1e5cc70524d65f789b166c1df1b43</cites><orcidid>0000-0003-1663-8378 ; 0000-0003-3397-8972 ; 0000-0002-1476-7531</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>230,314,776,780,881,3664,27903,27904</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/33500317$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Kowalczyk, Izabela</creatorcontrib><creatorcontrib>Lee, Chanjae</creatorcontrib><creatorcontrib>Schuster, Elisabeth</creatorcontrib><creatorcontrib>Hoeren, Josefine</creatorcontrib><creatorcontrib>Trivigno, Valentina</creatorcontrib><creatorcontrib>Riedel, Levin</creatorcontrib><creatorcontrib>Görne, Jessica</creatorcontrib><creatorcontrib>Wallingford, John B</creatorcontrib><creatorcontrib>Hammes, Annette</creatorcontrib><creatorcontrib>Feistel, Kerstin</creatorcontrib><title>Neural tube closure requires the endocytic receptor Lrp2 and its functional interaction with intracellular scaffolds</title><title>Development (Cambridge)</title><addtitle>Development</addtitle><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.</description><subject>Animals</subject><subject>Cell Membrane - metabolism</subject><subject>Cell Polarity</subject><subject>Endocytosis</subject><subject>Intracellular Space - metabolism</subject><subject>Low Density Lipoprotein Receptor-Related Protein-2 - deficiency</subject><subject>Low Density Lipoprotein Receptor-Related Protein-2 - metabolism</subject><subject>Mice</subject><subject>Mice, Inbred C57BL</subject><subject>Models, Biological</subject><subject>Morphogenesis</subject><subject>Neural Tube - embryology</subject><subject>Neural Tube - metabolism</subject><subject>Neural Tube - ultrastructure</subject><subject>Neuroepithelial Cells - metabolism</subject><subject>Prosencephalon - metabolism</subject><subject>Protein Binding</subject><subject>Xenopus</subject><subject>Xenopus Proteins - metabolism</subject><issn>0950-1991</issn><issn>1477-9129</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2021</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNpVkU9r3DAQxUVpaTZJL_0ARccScKqRLMu-FEpIk8DSXpqzkOVRV8VrbfQnId--2m4aktMwb368meER8hHYOfCWf5nw_hwGyVj_hqygVaoZgA9vyYpVsYFhgCNynNIfxpjolHpPjoSotAC1IvkHlmhmmsuI1M4hlYg04l3xERPNG6S4TME-Zm-rbHGXQ6TruOPULBP1OVFXFpt9WKqJXzJG86-jDz5v9kLtcZ7LbCJN1jgX5imdknfOzAk_PNUTcvv98tfFdbP-eXVz8W3dWKH63EgjbQdOImeWy1FaOUDrehwHg1wAB8QJUFqrmOTt1Emn-mGErrMwORhbcUK-Hnx3ZdziZHF_zqx30W9NfNTBeP16sviN_h3uteo7BqCqwecngxjuCqastz7t_zELhpI0b3voWtGLrqJnB9TGkFJE97wGmN7HpGtM-hBThT-9POwZ_Z-L-Atq05HC</recordid><startdate>20210126</startdate><enddate>20210126</enddate><creator>Kowalczyk, Izabela</creator><creator>Lee, Chanjae</creator><creator>Schuster, Elisabeth</creator><creator>Hoeren, Josefine</creator><creator>Trivigno, Valentina</creator><creator>Riedel, Levin</creator><creator>Görne, Jessica</creator><creator>Wallingford, John B</creator><creator>Hammes, Annette</creator><creator>Feistel, Kerstin</creator><general>The Company of Biologists Ltd</general><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7X8</scope><scope>5PM</scope><orcidid>https://orcid.org/0000-0003-1663-8378</orcidid><orcidid>https://orcid.org/0000-0003-3397-8972</orcidid><orcidid>https://orcid.org/0000-0002-1476-7531</orcidid></search><sort><creationdate>20210126</creationdate><title>Neural tube closure requires the endocytic receptor Lrp2 and its functional interaction with intracellular scaffolds</title><author>Kowalczyk, Izabela ; 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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.</abstract><cop>England</cop><pub>The Company of Biologists Ltd</pub><pmid>33500317</pmid><doi>10.1242/dev.195008</doi><orcidid>https://orcid.org/0000-0003-1663-8378</orcidid><orcidid>https://orcid.org/0000-0003-3397-8972</orcidid><orcidid>https://orcid.org/0000-0002-1476-7531</orcidid><oa>free_for_read</oa></addata></record> |
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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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