Novel role of Septin2 in Endothelial Cell Podosome Formation and Matrix Degradation

Abstract

In the initial phases of angiogenesis endothelial cells must degrade the extracellular matrix before migrating to alternative sites to form nascent vessels. The degradation of the matrix is performed by podosomes, actin rich structures that are regulated by Src family kinases. Here we report that the filamentous GTPase Septin2 is phosphorylated upon activation of Src and plays a critical role in Src‐mediated podosome formation and matrix degradation. We have identified that activation of Src induces phosphorylation of Septin2 and its translocation to the podosome structures in endothelial cells. Super resolution microscopy analysis further revealed that Septin2 localizes to the borders of podosome rosettes on the basal side of the cell. We have found that downregulation of Septin2 expression in endothelial cells inhibits Src‐mediated podosome formation as well as matrix degradation. Additionally, we have shown that Septin2 expression is necessary for endothelial cell invasion into a 3D collagen matrix, indicating a possible role for Septin2 in angiogenesis via regulation of podosome function. We are currently investigating the role of Septin2 in angiogenesis as well as the functional significance of Septin2 phosphorylation secondary to Src activation.