LAUSR

Endothelial cell-cell adherens junctions (AJs) supervise fundamental vascular functions, such as the control of permeability and transmigration of circulating leukocytes, and the maintenance of existing vessels and formation of new ones. These processes are often dysregulated in pathologies. However, the evidence that links dysfunction of endothelial AJs to human pathologies is mostly correlative. In this review, we present an update of the molecular organization of AJ complexes in endothelial cells (ECs) that is mainly based on observations from experimental models. Furthermore, we report in detail on a human pathology, cerebral cavernous malformation (CCM), which is initiated by loss-of-function mutations in the genes that encode the three cytoplasmic components of AJs (CCM1, CCM2, and CCM3). At present, these represent a unique example of mutations in components of endothelial AJs that cause human disease. We describe also how studies into the defects of AJs in CCM are shedding light on the crucial regulatory mechanisms and signaling activities of these endothelial structures. Although these observations are specific for CCM, they support the concept that dysfunction of endothelial AJs can directly contribute to human pathologies.