Journal
JOURNAL OF CELL SCIENCE
Volume 129, Issue 13, Pages 2586-2598Publisher
COMPANY BIOLOGISTS LTD
DOI: 10.1242/jcs.186585
Keywords
Podosomes; Endothelial cells; VEGF-A; Collagen-IV; Basement membrane
Categories
Funding
- Institut National de la Sante et de la Recherche Medicale (INSERM): the Ligue Contre le Cancer (Comite des Pyrenees Atlantiques)
- Fondation de France [00056836]
- Ligue Contre le Cancer
- Association pour la Recherche sur le Cancer
- French State of the 'Investments for the future' Program IdEx Bordeaux grant [ANR -10-10FX-03-02]
Ask authors/readers for more resources
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.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available