title: Sorting nexin 31 binds multiple β integrin cytoplasmic domains and regulates β1 integrin surface levels and stability.
abstract: Trafficking of α5β1 integrin to lysosomes and its subsequent degradation is influenced by ligand occupancy and the binding of SNX17 via its protein 4.1, ezrin, radixin, moesin (FERM) domain to the membrane-distal NPxY motif in the cytoplasmic domain of β1 integrin in early endosomes. Two other sorting nexin (SNX) family members, namely SNX27 and SNX31, share with SNX17 next to their obligate phox domain a FERM domain, which may enable them to bind β integrin tails. Here we report that, in addition to SNX17, SNX31 but not SNX27 binds several β integrin tails in early endosomes in a PI3 (phosphatidylinositide 3)-kinase-dependent manner. Similarly like SNX17, binding of SNX31 with β1 integrin tails in early endosomes occurs between the FERM domain and the membrane-distal NPxY motif in the β1 integrin cytoplasmic domain. Furthermore, expression of SNX31 rescues β1 integrin surface levels and stability in SNX17-depleted cells. In contrast to SNX17, expression of SNX31 is restricted and found highly expressed in bladder and melanoma tissue. Altogether, these results demonstrate that SNX31 is an endosomal regulator of β integrins with a restricted expression pattern.
authors.affiliation: Department of Molecular Medicine, Max Planck Institute of Biochemistry, Am Klopferspitz 18, 82152 Martinsried, Germany.
authors.forename: Hui-Yuan
authors.initials: HY
authors.lastname: Tseng
authors.affiliation: Department of Molecular Medicine, Max Planck Institute of Biochemistry, Am Klopferspitz 18, 82152 Martinsried, Germany.
authors.forename: Niko
authors.initials: N
authors.lastname: Thorausch
authors.affiliation: Department of Molecular Medicine, Max Planck Institute of Biochemistry, Am Klopferspitz 18, 82152 Martinsried, Germany.
authors.forename: Tilman
authors.initials: T
authors.lastname: Ziegler
authors.affiliation: Department of Dermatology, Mayo Clinic, Rochester, MN 55905, USA.
authors.forename: Alexander
authors.initials: A
authors.lastname: Meves
authors.affiliation: Department of Molecular Medicine, Max Planck Institute of Biochemistry, Am Klopferspitz 18, 82152 Martinsried, Germany.
authors.forename: Reinhard
authors.initials: R
authors.lastname: Fässler
authors.affiliation: Department of Molecular Medicine, Max Planck Institute of Biochemistry, Am Klopferspitz 18, 82152 Martinsried, Germany. Electronic address: rboettch@biochem.mpg.de.
authors.forename: Ralph T
authors.initials: RT
authors.lastname: Böttcher
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D045744:Cell Line, Tumor; D003593:Cytoplasm / Q000378:metabolism; D003598:Cytoskeletal Proteins / Q000378:metabolism; D011992:Endosomes / Q000378:metabolism; D005786:Gene Expression Regulation; D006801:Humans; D019012:Integrin beta1 / Q000378:metabolism*; D008565:Membrane Proteins / Q000378:metabolism; D051379:Mice; D018345:Mice, Knockout; D008840:Microfilament Proteins / Q000378:metabolism; D008969:Molecular Sequence Data; D011485:Protein Binding; D055550:Protein Stability; D017434:Protein Structure, Tertiary; D021122:Protein Subunits; D011993:Recombinant Fusion Proteins; D016415:Sequence Alignment; D058305:Sorting Nexins / Q000378:metabolism*; D000099149:Ezrin
chemical_list: D003598:Cytoskeletal Proteins; D019012:Integrin beta1; D008565:Membrane Proteins; D008840:Microfilament Proteins; D021122:Protein Subunits; D011993:Recombinant Fusion Proteins; D058305:Sorting Nexins; D000099149:Ezrin; C487895:SNX17 protein, human; C000594013:SNX31 protein, human; C071058:moesin; C071776:radixin
keywords: SNX17; SNX27; integrin trafficking; melanoma; protein turnover