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J Cell Sci. 2016 Jul 1;129(13):2586-98. doi: 10.1242/jcs.186585. Epub 2016 May 26.

VEGF-A stimulates podosome-mediated collagen-IV proteolysis in microvascular endothelial cells.

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Université de Bordeaux, 33 000 Bordeaux, France.
Université de Bordeaux, 33 000 Bordeaux, France INSERM U1045, 33 000 Bordeaux, France.
Université de Bordeaux, 33 000 Bordeaux, France INSERM U1045, 33 000 Bordeaux, France


Podosomes are dynamic cell-matrix contact structures that combine several key abilities, including adhesion, matrix degradation and mechanosensing. These actin-based cytoskeletal structures have been mostly studied in monocytic cells, but much less is known about those formed in other lineages. In this study, we characterise podosomes in capillary-derived microvascular endothelial cells. We identify two types of podosomes: constitutive podosomes that form in the absence of specific stimulation and induced podosomes that arise in response to the angiogenic factor VEGF-A. Constitutive and VEGF-A-induced podosomes share similar components but exhibit marked differences in terms of gelatinolytic activity. We also show that the extracellular matrix proteins laminin and collagen-IV are key determinants of the VEGF-A response, but neither collagen-I nor fibronectin are conducive for podosome induction. Moreover, only collagen-IV elicits the formation of proteolytically active podosomes through a mechanism involving increased Src phosphorylation, p190RhoGAP-B (also known as ARHGAP5) relocalisation and MT1-MMP (also known as MMP14) cell surface exposure at podosome sites. We hypothesise that by promoting podosome formation, VEGF-A enables endothelial cells to overcome the basement membrane barrier to allow sprouting outwards from the existing vasculature.


Basement membrane; Collagen-IV; Endothelial cells; Podosomes; VEGF-A

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