Protease Activated Receptor Signaling Is Required for African Trypanosome Traversal of Human Brain Microvascular Endothelial Cells
Figure 5
Proposed model for African trypanosome-induced BBB dysfunction.
We hypothesize that parasite proteases trigger GPCRs (i.e. PARs?) via Gαq activation, which leads to PLC-mediated Ca2+ release from intracellular stores. The increase in intracellular calcium leads to calmodulin (CaM) activation of myosin light chain kinase (MLCK), ultimately leading to cytoskeletal changes and barrier dysfunction. Ca2+-independent activation of the cytoskeleton mediated by Ras-superfamily GTPases (i.e. RhoA) is also possible via p63RhoGEF. Parasite and/or host-derived proteases may also contribute by degrading or altering adherens junction (AJ) and tight junction (TJ) proteins.