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

• Published in: Nature cell biology Vol. 14; no. 6; pp. 584 - 592
• Main Authors: Böttcher, Ralph Thomas, Stremmel, Christopher, Meves, Alexander, Meyer, Hannelore, Widmaier, Moritz, Tseng, Hui-Yuan, Fässler, Reinhard
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 01.06.2012
• Subjects: 631/80/313/1776; 631/80/474/1624; 631/80/79/1236; Animals; Biomedical and Life Sciences; Cancer Research; Cell Biology; Developmental Biology; Embryo, Mammalian - metabolism; Endosomes - metabolism; Integrin beta1 - genetics; Integrin beta1 - metabolism; Life Sciences; Lysosomes - metabolism; Mice; Protein Binding; RNA, Messenger - metabolism; Sorting Nexins - genetics; Sorting Nexins - metabolism; Stem Cells
• ISSN: 1465-7392; 1476-4679
• DOI: 10.1038/ncb2501

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. Integrin internalization through the endosomal pathway can lead either to recycling back to the surface or to lysosomal degradation. Faessler and colleagues now show that, following internalization, β1 integrins are bound by sorting nexin 17 in early endosomes to prevent integrin degradation in lysosomes and to promote surface recycling.