Sorting nexin 17 prevents lysosomal degradation of β1 integrins by binding to the β1-integrin tail

Integrin functions are controlled by regulating their affinity for ligand, and by the efficient recycling of intact integrins through endosomes. Here we demonstrate that the Kindlin-binding site in the beta(1)-integrin cytoplasmic domain serves as a molecular switch enabling the sequential binding of two FERM-domain-containing proteins in different cellular compartments. When beta(1) integrins are at the plasma membrane, Kindlins control ligand-binding affinity. However, when they are internalized, Kindlins dissociate from integrins and sorting nexin 17 (SNX17) is recruited to free beta(1)-integrin tails in early endosomes to prevent beta(1)-integrin degradation, leading to their recycling back to the cell surface. Our results identify SNX17 as a beta(1)-integrin-tail-binding protein that interacts with the free Kindlin-binding site in endosomes to stabilize beta(1) integrins, resulting in their recycling to the cell surface where they can be reused.