Sorting nexin 17 prevents lysosomal degradation of β1 integrins by binding to the β 1-integrin tail

Ralph Thomas Böttcher, Christopher Stremmel, Alexander Meves, Hannelore Meyer, Moritz Widmaier, Hui Yuan Tseng, Reinhard Fässler

Research output: Contribution to journalArticle

121 Scopus citations

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 β 1-integrin cytoplasmic domain serves as a molecular switch enabling the sequential binding of two FERM-domain-containing proteins in different cellular compartments. When β 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 β 1-integrin tails in early endosomes to prevent β 1-integrin degradation, leading to their recycling back to the cell surface. Our results identify SNX17 as a β 1-integrin-tail- binding protein that interacts with the free Kindlin-binding site in endosomes to stabilize β 1 integrins, resulting in their recycling to the cell surface where they can be reused.

Original languageEnglish (US)
Pages (from-to)584-592
Number of pages9
JournalNature Cell Biology
Volume14
Issue number6
DOIs
StatePublished - Jun 1 2012

ASJC Scopus subject areas

  • Cell Biology

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    Böttcher, R. T., Stremmel, C., Meves, A., Meyer, H., Widmaier, M., Tseng, H. Y., & Fässler, R. (2012). Sorting nexin 17 prevents lysosomal degradation of β1 integrins by binding to the β 1-integrin tail. Nature Cell Biology, 14(6), 584-592. https://doi.org/10.1038/ncb2501