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

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

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Embryo, Mammalian / metabolism
  • Endosomes / metabolism
  • Integrin beta1 / genetics
  • Integrin beta1 / metabolism*
  • Lysosomes / metabolism*
  • Mice
  • Protein Binding
  • RNA, Messenger / metabolism
  • Sorting Nexins / genetics
  • Sorting Nexins / metabolism*


  • Integrin beta1
  • RNA, Messenger
  • Snx17 protein, mouse
  • Sorting Nexins