Autocrine fibronectin directs matrix assembly and crosstalk between cell-matrix and cell-cell adhesion in vascular endothelial cells

作者：Cseh Botond; Fernandez Sauze Samantha; Grall Dominique; Schaub Sebastien; Doma Eszter; Van Obberghen Schilling Ellen^*

来源：Journal of Cell Science, 2010, 123(22): 3989-3999.

DOI：10.1242/jcs.073346

• Adhesion
• Fibrillogenesis
• Fibronectin
• Vascular endothelial cell

Cellular fibronectin (cFN) variants harboring extra FN type 3 repeats, namely extra domains B and A, are major constituents of the extracellular matrix around newly forming blood vessels during development and angiogenesis. Their expression is induced by angiogenic stimuli and their assembly into fibrillar arrays is driven by cell-generated tension at alpha 5 beta 1 integrin-based adhesions. Here, we examined the role and functional redundancy of cFN variants in cultured endothelial cells by isoform-selective RNA interference. We show that FN fibrillogenesis is a cell-autonomous process whereby basally directed secretion and assembly of cellular FN are tightly coupled events that play an important role not only in signaling at cell-matrix adhesions but also at cell-cell contacts. Silencing of cFN variants differentially affects integrin usage, cell spreading, motility and capillary morphogenesis in vitro. cFN-deficient cells undergo a switch from alpha 5 beta 1-to alpha v beta 3-based adhesion, accompanied by a Src-regulated disruption of adherens junctions. These studies identify a crucial role for autocrine FN in subendothelial matrix assembly and junctional integrity that provides spatially and temporally restricted control of endothelial plasticity during angiogenic blood vessel remodeling.

• 出版日期2010-11-15