Heart of glass anchors Rasip1 at endothelial cell-cell junctions to support vascular integrity
Heart of Glass (HEG1), a transmembrane receptor, and Rasip1, an endothelial-specific Rap1-binding protein, are both essential for cardiovascular development. Here we performed a proteomic screen for novel HEG1 interactors and report that HEG1 binds directly to Rasip1. Rasip1 localizes to forming end...
| Main Authors: | , , , , , |
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| Format: | Article |
| Language: | English |
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eLife Sciences Publications Ltd
2016-01-01
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| Series: | eLife |
| Subjects: | |
| Online Access: | https://elifesciences.org/articles/11394 |
| _version_ | 1811236991551930368 |
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| author | Bart-Jan de Kreuk Alexandre R Gingras James DR Knight Jian J Liu Anne-Claude Gingras Mark H Ginsberg |
| author_facet | Bart-Jan de Kreuk Alexandre R Gingras James DR Knight Jian J Liu Anne-Claude Gingras Mark H Ginsberg |
| author_sort | Bart-Jan de Kreuk |
| collection | DOAJ |
| description | Heart of Glass (HEG1), a transmembrane receptor, and Rasip1, an endothelial-specific Rap1-binding protein, are both essential for cardiovascular development. Here we performed a proteomic screen for novel HEG1 interactors and report that HEG1 binds directly to Rasip1. Rasip1 localizes to forming endothelial cell (EC) cell-cell junctions and silencing HEG1 prevents this localization. Conversely, mitochondria-targeted HEG1 relocalizes Rasip1 to mitochondria in cells. The Rasip1-binding site in HEG1 contains a 9 residue sequence, deletion of which abrogates HEG1’s ability to recruit Rasip1. HEG1 binds to a central region of Rasip1 and deletion of this domain eliminates Rasip1’s ability to bind HEG1, to translocate to EC junctions, to inhibit ROCK activity, and to maintain EC junctional integrity. These studies establish that the binding of HEG1 to Rasip1 mediates Rap1-dependent recruitment of Rasip1 to and stabilization of EC cell-cell junctions. |
| first_indexed | 2024-04-12T12:18:16Z |
| format | Article |
| id | doaj.art-dcda1f2adf504976a355377abd7c7903 |
| institution | Directory Open Access Journal |
| issn | 2050-084X |
| language | English |
| last_indexed | 2024-04-12T12:18:16Z |
| publishDate | 2016-01-01 |
| publisher | eLife Sciences Publications Ltd |
| record_format | Article |
| series | eLife |
| spelling | doaj.art-dcda1f2adf504976a355377abd7c79032022-12-22T03:33:23ZengeLife Sciences Publications LtdeLife2050-084X2016-01-01510.7554/eLife.11394Heart of glass anchors Rasip1 at endothelial cell-cell junctions to support vascular integrityBart-Jan de Kreuk0Alexandre R Gingras1James DR Knight2Jian J Liu3Anne-Claude Gingras4Mark H Ginsberg5https://orcid.org/0000-0002-5685-5417Department of Medicine, University of California, San Diego, San Diego, United StatesDepartment of Medicine, University of California, San Diego, San Diego, United StatesLunenfeld-Tanenbaum Research Institute, Mount Sinai Hospital, Toronto, CanadaDepartment of Medicine, University of California, San Diego, San Diego, United StatesLunenfeld-Tanenbaum Research Institute, Mount Sinai Hospital, Toronto, Canada; Department of Molecular Genetics, University of Toronto, Toronto, CanadaDepartment of Medicine, University of California, San Diego, San Diego, United StatesHeart of Glass (HEG1), a transmembrane receptor, and Rasip1, an endothelial-specific Rap1-binding protein, are both essential for cardiovascular development. Here we performed a proteomic screen for novel HEG1 interactors and report that HEG1 binds directly to Rasip1. Rasip1 localizes to forming endothelial cell (EC) cell-cell junctions and silencing HEG1 prevents this localization. Conversely, mitochondria-targeted HEG1 relocalizes Rasip1 to mitochondria in cells. The Rasip1-binding site in HEG1 contains a 9 residue sequence, deletion of which abrogates HEG1’s ability to recruit Rasip1. HEG1 binds to a central region of Rasip1 and deletion of this domain eliminates Rasip1’s ability to bind HEG1, to translocate to EC junctions, to inhibit ROCK activity, and to maintain EC junctional integrity. These studies establish that the binding of HEG1 to Rasip1 mediates Rap1-dependent recruitment of Rasip1 to and stabilization of EC cell-cell junctions.https://elifesciences.org/articles/11394Rasip1Heart of Glassendothelial cellsRho KinaseRap1 |
| spellingShingle | Bart-Jan de Kreuk Alexandre R Gingras James DR Knight Jian J Liu Anne-Claude Gingras Mark H Ginsberg Heart of glass anchors Rasip1 at endothelial cell-cell junctions to support vascular integrity eLife Rasip1 Heart of Glass endothelial cells Rho Kinase Rap1 |
| title | Heart of glass anchors Rasip1 at endothelial cell-cell junctions to support vascular integrity |
| title_full | Heart of glass anchors Rasip1 at endothelial cell-cell junctions to support vascular integrity |
| title_fullStr | Heart of glass anchors Rasip1 at endothelial cell-cell junctions to support vascular integrity |
| title_full_unstemmed | Heart of glass anchors Rasip1 at endothelial cell-cell junctions to support vascular integrity |
| title_short | Heart of glass anchors Rasip1 at endothelial cell-cell junctions to support vascular integrity |
| title_sort | heart of glass anchors rasip1 at endothelial cell cell junctions to support vascular integrity |
| topic | Rasip1 Heart of Glass endothelial cells Rho Kinase Rap1 |
| url | https://elifesciences.org/articles/11394 |
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