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.