Heart of glass anchors Rasip1 at endothelial cell-cell junctions to support vascular integrity

ELife
Bart-Jan de KreukMark H Ginsberg

Abstract

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.

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Citations

Feb 18, 2017·Current Opinion in Hematology·Maria Grazia LampugnaniNoemi Rudini
Feb 9, 2017·Current Opinion in Hematology·Magdalena Chrzanowska-Wodnicka
Aug 31, 2017·Cold Spring Harbor Perspectives in Biology·Maria Grazia LampugnaniCostanza Giampietro
May 30, 2019·Physiological Reviews·Nina WettschureckStefan Offermanns
Nov 22, 2017·The Journal of Biological Chemistry·Carla J RamosDavid A Antonetti
Oct 28, 2019·Clinical Science·Brittany Dewdney, Lionel Hebbard
Jan 24, 2020·International Journal of Molecular Sciences·Shu WeiLe Shen
Nov 26, 2020·Open Biology·Valerie L Su, David A Calderwood
May 13, 2021·FASEB BioAdvances·Miguel Alejandro Lopez-RamirezAlexandre R Gingras
Jun 23, 2021·Seminars in Cell & Developmental Biology·Li-Kun Phng, Heinz-Georg Belting
Jun 25, 2021·Circulation Research·Daniel A SnellingsMark L Kahn
Aug 13, 2021·Development·Minkyoung LeeHeinz-Georg Belting

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Datasets Mentioned

BETA
PXD003328

Methods Mentioned

BETA
GTPases
affinity purification
Confocal Microscopy
Immuno-Precipitation
co-immunoprecipitation
flow cytometry
size exclusion chromatography
Isothermal Titration Calorimetry
gel filtration
transfection

Software Mentioned

Protein Homology / analogY Recognition Engine ( PHYRE
Mascot
MicroCal Origin
PISA ( Proteins , Interfaces , Structures and Assemblies )
CellQuest
Radil
SAINTexpress
R

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