Golgi-Associated Cpla2 Alpha Regulates Endothelial Cell-Cell Junction Integrity By Controlling The Trafficking Of Transmembrane Junction Proteins

In endothelial cells specifically, cPLA2 alpha translocates from the cytoplasm to the Golgi complex in response to cell confluence. Considering the link between confluence and cell-cell junction formation, and the emerging role of cPLA2 alpha in intracellular trafficking, we tested whether Golgi-associated cPLA2 alpha is involved in the trafficking of junction proteins. Here, we show that the redistribution of cPLA2 alpha from the cytoplasm to the Golgi correlates with adherens junction maturation and occurs before tight junction formation. Disruption of adherens junctions using a blocking anti-VE-cadherin antibody reverses the association of cPLA2 alpha with the Golgi. Silencing of cPLA2 alpha and inhibition of cPLA2 alpha enzymatic activity using various inhibitors result in the diminished presence of the transmembrane junction proteins VE-cadherin, occludin, and claudin-5 at cell-cell contacts, and in their accumulation at the Golgi. Altogether, our data support the idea that VE-cadherin triggers the relocation of cPLA2 alpha to the Golgi and that in turn, Golgi-associated cPLA2 alpha regulates the transport of transmembrane junction proteins through or from the Golgi, thereby controlling the integrity of endothelial cell-cell junctions.