title: Sorting nexin 17 prevents lysosomal degradation of β1 integrins by binding to the β1-integrin tail.
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.
authors.affiliation: Department of Molecular Medicine, Max Planck Institute for Biochemistry, 82152 Martinsried, Germany.
authors.forename: Ralph Thomas
authors.initials: RT
authors.lastname: Böttcher
authors.forename: Christopher
authors.initials: C
authors.lastname: Stremmel
authors.forename: Alexander
authors.initials: A
authors.lastname: Meves
authors.forename: Hannelore
authors.initials: H
authors.lastname: Meyer
authors.forename: Moritz
authors.initials: M
authors.lastname: Widmaier
authors.forename: Hui-Yuan
authors.initials: HY
authors.lastname: Tseng
authors.forename: Reinhard
authors.initials: R
authors.lastname: Fässler
mesh_terms: D000818:Animals; D004622:Embryo, Mammalian / Q000378:metabolism; D011992:Endosomes / Q000378:metabolism; D019012:Integrin beta1 / Q000235:genetics / Q000378:metabolism*; D008247:Lysosomes / Q000378:metabolism*; D051379:Mice; D011485:Protein Binding; D012333:RNA, Messenger / Q000378:metabolism; D058305:Sorting Nexins / Q000235:genetics / Q000378:metabolism*
chemical_list: D019012:Integrin beta1; D012333:RNA, Messenger; C465498:Snx17 protein, mouse; D058305:Sorting Nexins