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MAGP ‐1 and fibronectin control EGFL 7 functions by driving its deposition into distinct endothelial extracellular matrix locations
Author(s) -
Villain Gaëlle,
Lelievre Etienne,
Broekelmann Tom,
Gayet Odile,
Havet Chantal,
Werkmeister Elisabeth,
Mecham Robert,
Dusetti Nelson,
Soncin Fabrice,
Mattot Virginie
Publication year - 2018
Publication title -
the febs journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.981
H-Index - 204
eISSN - 1742-4658
pISSN - 1742-464X
DOI - 10.1111/febs.14680
Subject(s) - extracellular matrix , microbiology and biotechnology , fibronectin , endothelial stem cell , lysyl oxidase , notch signaling pathway , chemistry , cell adhesion molecule , cell adhesion , integrin , signal transduction , biology , cell , biochemistry , in vitro
The extracellular matrix ( ECM ) is essential to provide mechanical support to tissues but is also a bioactive edifice which controls cell behavior. Cell signaling generated by ECM components through integrin‐mediated contacts, modulates cell biological activity. In addition, by sequestrating or releasing growth factors, the ECM is an active player of physiological and pathological processes such as vascular development. EGFL 7 is mainly expressed during blood vessel development and is deposited in the ECM after secretion by endothelial cells. While EGFL 7 is known to control various endothelial cell molecular mechanisms [i.e., the repression of endothelial‐derived lysyl oxidase ( LOX ) enzyme, the regulation of the Notch pathway, and the expression of leukocyte adhesion molecules and of RHOA by endothelial cells], it is not established whether EGFL 7 functions when bound to the ECM . Here, we show that microfibrillar‐associated glycoprotein‐1 ( MAGP ‐1) and fibronectin drive the deposition of EGFL 7 into both fibers and individual aggregates in endothelial ECM . Although EGFL 7 does not need to be docked into the ECM to control endothelial adhesion molecule expression, the ECM accumulation of EGFL 7 is required for its regulation of LOX activity and of HEY 2 expression along the Notch pathway. The interaction of EGFL 7 with MAGP ‐1 is necessary for LOX activity repression by EGFL 7 while it does not participate in the control of the Notch pathway by this protein. Altogether, this study highlights the roles played by EGFL 7 in controlling various endothelial molecular mechanisms upon its localization and shows how the ECM can modulate its functions.