Protein phosphorylation and the regulation of cell-cell junctions in brain endothelial cells

Endothelial cells lining the capillaries of the brain have two properties that distinguish them from their peripheral counterparts: (1) tight junctions of extremely low permeability; and (2) low rates of fluid-phase endocytosis. In combination, these features limit the nonspecific flux of ions, proteins, and other substances into the central nervous system environment, creating the blood-brain barrier. This barrier is not immutable. Tight junction permeability can be rapidly increased, which may play a role in the development of a variety of brain pathologies. We have therefore been interested in mechanisms regulating junctional permeability and strategies for interfering with this regulation. What is becoming increasingly apparent is that junctions are not passive mechanical entities; rather, they are targets for a variety of signaling pathways.