Sorting nexin 17 prevents lysosomal degradation of β1 integrins by binding to the β1-integrin tail
RT Böttcher, C Stremmel, A Meves, H Meyer… - Nature cell …, 2012 - nature.com
RT Böttcher, C Stremmel, A Meves, H Meyer, M Widmaier, HY Tseng, R Fässler
Nature cell biology, 2012•nature.comIntegrin 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 β1-integrin cytoplasmic domain serves as a molecular switch enabling the
sequential binding of two FERM-domain-containing proteins in different cellular
compartments. When β1 integrins are at the plasma membrane, Kindlins control ligand-
binding affinity. However, when they are internalized, Kindlins dissociate from integrins and …
recycling of intact integrins through endosomes. Here we demonstrate that the Kindlin-
binding site in the β1-integrin cytoplasmic domain serves as a molecular switch enabling the
sequential binding of two FERM-domain-containing proteins in different cellular
compartments. When β1 integrins are at the plasma membrane, Kindlins control ligand-
binding affinity. However, when they are internalized, Kindlins dissociate from integrins and …
Abstract
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 β1-integrin cytoplasmic domain serves as a molecular switch enabling the sequential binding of two FERM-domain-containing proteins in different cellular compartments. When β1 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 β1-integrin tails in early endosomes to prevent β1-integrin degradation, leading to their recycling back to the cell surface. Our results identify SNX17 as a β1-integrin-tail-binding protein that interacts with the free Kindlin-binding site in endosomes to stabilize β1 integrins, resulting in their recycling to the cell surface where they can be reused.
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