MAGI1 localizes to mature focal adhesion and modulates endothelial cell adhesion, migration and angiogenesis

Begoña Alday-Parejo; Kedar Ghimire; Oriana Coquoz; Gioele W Albisetti; Luca Tamò; Jelena Zaric; Jimmy Stalin; Curzio Rüegg

doi:10.1080/19336918.2021.1911472

MAGI1 localizes to mature focal adhesion and modulates endothelial cell adhesion, migration and angiogenesis

Cell Adh Migr. 2021 Dec;15(1):126-139. doi: 10.1080/19336918.2021.1911472.

Authors

Begoña Alday-Parejo¹, Kedar Ghimire^{1

2}, Oriana Coquoz¹, Gioele W Albisetti^{1

3}, Luca Tamò^{1

4}, Jelena Zaric^{1

5}, Jimmy Stalin¹, Curzio Rüegg¹

Affiliations

¹ Laboratory of Experimental and Translational Oncology, Pathology, Department of Oncology, Microbiology and Immunology, Faculty of Sciences and Medicine, University of Fribourg, Fribourg, Switzerland.
² Westmead Institute for Medical Research, University of Sydney, Sydney, Australia.
³ Institute of Pharmacology and Toxicology, Section of Neuropharmacology, University of Zürich, Zürich, Switzerland.
⁴ Clinical Trials Unit, University of Bern, Bern, Switzerland.
⁵ Swiss Institute for Experimental Cancer Research, Ecole Polytechnique Fédérale De Lausanne, Lausanne, Switzerland.

Abstract

MAGI1 is an intracellular adaptor protein that stabilizes cell junctions and regulates epithelial and endothelial integrity. Here, we report that that in endothelial cells MAGI1 colocalizes with paxillin, β3-integrin, talin 1, tensin 3 and α-4-actinin at mature focal adhesions and actin stress fibers, and regulates their dynamics. Downregulation of MAGI1 reduces focal adhesion formation and maturation, cell spreading, actin stress fiber formation and RhoA/Rac1 activation. MAGI1 silencing increases phosphorylation of paxillin at Y118, an indicator of focal adhesion turnover. MAGI1 promotes integrin-dependent endothelial cells adhesion to ECM, reduces invasion and tubulogenesisin vitro and suppresses angiogenesis in vivo. Our results identify MAGI1 as anovel component of focal adhesions, and regulator of focal adhesion dynamics, cell adhesion, invasion and angiogenesis.

Keywords: Cell adhesion; cytoskeleton; extracellular matrix; migration; signaling; stress fibers.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Actinin / metabolism
Adaptor Proteins, Signal Transducing / metabolism*
Animals
Cell Adhesion / physiology*
Cell Adhesion Molecules / metabolism*
Cell Movement
Endothelial Cells / metabolism*
Focal Adhesion Protein-Tyrosine Kinases / metabolism
Focal Adhesions / metabolism*
Guanylate Kinases / metabolism*
Humans
Integrin beta3 / metabolism
Mice
Mice, Transgenic
Neovascularization, Physiologic*
Paxillin / metabolism
Phosphorylation
Stress, Mechanical
Talin / metabolism
Tensins / metabolism
rac1 GTP-Binding Protein / metabolism
rhoA GTP-Binding Protein / metabolism

Substances

Adaptor Proteins, Signal Transducing
Cell Adhesion Molecules
Integrin beta3
Paxillin
Talin
Tensins
Actinin
Focal Adhesion Protein-Tyrosine Kinases
Guanylate Kinases
MAGI1 protein, human
rac1 GTP-Binding Protein
rhoA GTP-Binding Protein

Grants and funding

This work was funded by the Krebsforschung Schweiz [KSF-4400-02-2018];FP7 Small Artery Marie Curie Initial Training Network [235711];FP7 Small Artery Marie Curie Initial Training Network [606998];Schweizerische Herzstiftung [FF18115];Swiss National Science Foundation [31003A_179248];