The Effects of Cavin-2 on Angiogenesis

Abstract

Caveolae are bulb-shaped invaginations about 50-60nm in size on the plasma membrane of mammalian cells that play a key role in cell signaling, endocytosis, plasma membrane adaptations, and lipid homeostasis. Caveolae are known to be important in angiogenesis and are found in the microvasculature of the skeletal muscle, heart and lung, making up to 60% of the plasma membrane. While the mechanisms of caveolae regulation are not completely understood, Cavin family proteins appear to be critical regulators of caveolae. Cavin proteins form subcomplexes through homo- and hetero-oligomerization which regulate caveolae dynamics. Cavin-2, also known as serum deprivation-response protein, or SDPR, is a key regulator of caveolae dynamics by binding to Cavin-1 and introducing membrane tubules. To discover genes important for the transition of endothelial cells from a quiescent to an activated state, a switch that is critical for initiation of angiogenesis, we performed RNA sequencing analysis comparing unstimulated to activated, invading endothelial cells using a three-dimensional assay that mimics angiogenesis. We found expression of Cavin-2 was downregulated 73% in invading cells compared to non-invading cells. This study tested whether Cavin-2 might suppress endothelial sprouting responses. We found that overexpression of Cavin-2 had no statistically significant effect on cell invasion using this three-dimensional model of angiogenesis, indicating that Cavin-2 does not have a suppressive effect on endothelial sprout initiation.