Back to Search
Start Over
Septin2 mediates podosome maturation and endothelial cell invasion associated with angiogenesis
- Source :
- The Journal of Cell Biology
- Publication Year :
- 2019
- Publisher :
- Rockefeller University Press, 2019.
-
Abstract
- Podosomal remodeling of the extracellular matrix by endothelial cells is a key step facilitating sprouting angiogenesis. Collins et al. present Septin2 as a previously unknown facet of the complex regulatory mechanism governing podosome function and endothelial cell invasion.<br />Podosomes are compartmentalized actin-rich adhesions, defined by their ability to locally secrete proteases and remodel extracellular matrix. Matrix remodeling by endothelial podosomes facilitates invasion and thereby vessel formation. However, the mechanisms underlying endothelial podosome formation and function remain unclear. Here, we demonstrate that Septin2, Septin6, and Septin7 are required for maturation of nascent endothelial podosomes into matrix-degrading organelles. We show that podosome development occurs through initial mobilization of the scaffolding protein Tks5 and F-actin accumulation, followed by later recruitment of Septin2. Septin2 localizes around the perimeter of podosomes in close proximity to the basolateral plasma membrane, and phosphoinositide-binding residues of Septin2 are required for podosome function. Combined, our results suggest that the septin cytoskeleton forms a diffusive barrier around nascent podosomes to promote their maturation. Finally, we show that Septin2-mediated regulation of podosomes is critical for endothelial cell invasion associated with angiogenesis. Therefore, targeting of Septin2-mediated podosome formation is a potentially attractive anti-angiogenesis strategy.
- Subjects :
- Scaffold protein
Podosome
Angiogenesis
Neovascularization, Physiologic
Cell Cycle Proteins
Biology
Extracellular matrix
03 medical and health sciences
0302 clinical medicine
Cell Movement
Report
Morphogenesis
Animals
Humans
Actin
Research Articles
Cells, Cultured
030304 developmental biology
0303 health sciences
Endothelial Cells
Cell Biology
Basolateral plasma membrane
Cell biology
Extracellular Matrix
Endothelial stem cell
Actin Cytoskeleton
Adaptor Proteins, Vesicular Transport
Podosomes
030217 neurology & neurosurgery
Septins
Septin cytoskeleton
Subjects
Details
- Language :
- English
- ISSN :
- 15408140 and 00219525
- Volume :
- 219
- Issue :
- 2
- Database :
- OpenAIRE
- Journal :
- The Journal of Cell Biology
- Accession number :
- edsair.doi.dedup.....df01fa9e33fcf41fced4548c18ddd07d