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...

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Bibliographic Details
Published in:eLife 2016-01, Vol.5, p.e11394-e11394
Main Authors: de Kreuk, Bart-Jan, Gingras, Alexandre R, Knight, James Dr, Liu, Jian J, Gingras, Anne-Claude, Ginsberg, Mark H
Format: Article
Language:English
Subjects:
Cell adhesion & migration
Cell Biology
Cell interaction
Cell junctions
Cell Line
Clonal deletion
Developmental Biology and Stem Cells
Endothelial cells
Endothelial Cells - physiology
Heart
Heart of Glass
Humans
Intercellular Junctions - physiology
Intracellular Signaling Peptides and Proteins - metabolism
Kinases
Localization
Mass spectrometry
Membrane proteins
Membrane Proteins - metabolism
Mitochondria
Observations
Physiological aspects
Protein Binding
Proteins
Rap1
Rap1 protein
Rasip1
Rho Kinase
Scientific imaging
Software
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Summary: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.
ISSN:2050-084X
2050-084X
DOI:10.7554/elife.11394