Sorting nexin 17 prevents lysosomal degradation of β1 integrins by binding to the β1-integrin tail - PubMed (original) (raw)

. 2012 May 6;14(6):584-92.

doi: 10.1038/ncb2501.

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

Ralph Thomas Böttcher et al. Nat Cell Biol. 2012.

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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References

    1. Mol Cell Biol. 2004 Feb;24(4):1505-15 - PubMed
    1. Exp Cell Res. 2006 Oct 1;312(16):3142-51 - PubMed
    1. J Biol Chem. 2008 Apr 25;283(17):11501-8 - PubMed
    1. Proc Natl Acad Sci U S A. 2000 Oct 24;97(22):12227-32 - PubMed
    1. Nat Med. 2009 Mar;15(3):300-5 - PubMed

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