Molecular components regulating WPB excytosis. In resting endothelial cells WPBs are linked to microtubules and the actin cytoskeleton (1). Plus end directed movement of WPBs along microtubules is mediated by the motor protein kinesin. WPB are anchored to the actin cytoskeleton by the Rab27A/MyRIP complex (2). Ligand binding to G-protein coupled receptors initiates signal transduction pathways (3). G-protein–coupled receptors are subsequently internalized in a β-arrestin-mediated manner. Dissociation of the RalGDS/β-arrestin liberates RalGDS, which activates the small GTPase Ral. Activation of Ral mediates assembly of the exocyst complex (4). Simultaneously, Ral-dependent activation of phospholipase D1 induces accumulation of fusogenic lipids (5) that facilitate fusion of WPBs after the Munc18c-assisted assembly of the SNARE-complex (6). After stimulation of endothelial cells with cAMP-elevating agonists dynein-mediated minus-end directed movement of WPBs along microtubule promotes clustering of WPBs at the MTOC (7).