FIGURE 8.

Proposed itineraries of α5β1 integrin in endothelial cells with and without syntaxin 6 function. 1, α5 and β1 integrin complexes are co-internalized from the cell surface. 2, the complexes are transported to EEA1-positive EEs. 3, α5β1 complexes are transported through the perinuclear recycling compartment (PNRC) (recycling pathway) for delivery to the PM. Loss of syntaxin 6 function blocks the transport of α5β1 integrin through the recycling pathway. In the absence of syntaxin 6 function: 4, the pool of ubiquitinated α5 integrin within the EE increases, and α5β1 complexes are transported to LEs/lysosomes for degradation; and 5, levels of α5β1 integrin at the cell surface are reduced, leading to impaired cell adhesion, migration, and spreading on fibronectin.