The oxysterol-binding protein homologue ORP1L interacts with Rab7 and alters functional properties of late endocytic compartments

Marie Johansson, Markku Lehto, Kimmo Tanhuanpää, Timothy L Cover, Vesa M Olkkonen

    Tutkimustuotos: ArtikkelijulkaisuArtikkeliTieteellinenvertaisarvioitu

    Kuvaus

    ORP1L is a member of the human oxysterol-binding protein (OSBP) family. ORP1L localizes to late endosomes (LEs)/lysosomes, colocalizing with the GTPases Rab7 and Rab9 and lysosome-associated membrane protein-1. We demonstrate that ORP1L interacts physically with Rab7, preferentially with its GTP-bound form, and provide evidence that ORP1L stabilizes GTP-bound Rab7 on LEs/lysosomes. The Rab7-binding determinant is mapped to the ankyrin repeat (ANK) region of ORP1L. The pleckstrin homology domain (PHD) of ORP1L binds phosphoinositides with low affinity and specificity. ORP1L, ANK- and ANK+PHD fragments induce perinuclear clustering of LE/lysosomes. This is dependent on an intact microtubule network and a functional dynein/dynactin motor complex. The dominant inhibitory Rab7 mutant T22N reverses the LE clustering, suggesting that the effect is dependent on active Rab7. Transport of fluorescent dextran to LEs is inhibited by overexpression of ORP1L. Overexpression of ORP1L, and in particular the N-terminal fragments of ORP1L, inhibits vacuolation of LE caused by Helicobacter pylori toxin VacA, a process also involving Rab7. The present study demonstrates that ORP1L binds to Rab7, modifies its functional cycle, and can interfere with LE/lysosome organization and endocytic membrane trafficking. This is the first report of a direct connection between the OSBP-related protein family and the Rab GTPases.
    Alkuperäiskielienglanti
    LehtiMolecular Biology of the Cell
    Vuosikerta16
    Sivut5480-5492
    Sivumäärä13
    ISSN1059-1524
    DOI - pysyväislinkit
    TilaJulkaistu - 2005
    OKM-julkaisutyyppiA1 Alkuperäisartikkeli tieteellisessä aikakauslehdessä, vertaisarvioitu

    Lainaa tätä

    Johansson, Marie ; Lehto, Markku ; Tanhuanpää, Kimmo ; Cover, Timothy L ; Olkkonen, Vesa M. / The oxysterol-binding protein homologue ORP1L interacts with Rab7 and alters functional properties of late endocytic compartments. Julkaisussa: Molecular Biology of the Cell. 2005 ; Vuosikerta 16. Sivut 5480-5492.
    @article{1938290837d74585b106a9b9a6bc7efa,
    title = "The oxysterol-binding protein homologue ORP1L interacts with Rab7 and alters functional properties of late endocytic compartments",
    abstract = "ORP1L is a member of the human oxysterol-binding protein (OSBP) family. ORP1L localizes to late endosomes (LEs)/lysosomes, colocalizing with the GTPases Rab7 and Rab9 and lysosome-associated membrane protein-1. We demonstrate that ORP1L interacts physically with Rab7, preferentially with its GTP-bound form, and provide evidence that ORP1L stabilizes GTP-bound Rab7 on LEs/lysosomes. The Rab7-binding determinant is mapped to the ankyrin repeat (ANK) region of ORP1L. The pleckstrin homology domain (PHD) of ORP1L binds phosphoinositides with low affinity and specificity. ORP1L, ANK- and ANK+PHD fragments induce perinuclear clustering of LE/lysosomes. This is dependent on an intact microtubule network and a functional dynein/dynactin motor complex. The dominant inhibitory Rab7 mutant T22N reverses the LE clustering, suggesting that the effect is dependent on active Rab7. Transport of fluorescent dextran to LEs is inhibited by overexpression of ORP1L. Overexpression of ORP1L, and in particular the N-terminal fragments of ORP1L, inhibits vacuolation of LE caused by Helicobacter pylori toxin VacA, a process also involving Rab7. The present study demonstrates that ORP1L binds to Rab7, modifies its functional cycle, and can interfere with LE/lysosome organization and endocytic membrane trafficking. This is the first report of a direct connection between the OSBP-related protein family and the Rab GTPases.",
    author = "Marie Johansson and Markku Lehto and Kimmo Tanhuanp{\"a}{\"a} and Cover, {Timothy L} and Olkkonen, {Vesa M}",
    year = "2005",
    doi = "10.1091/mbc.E05-03-0189",
    language = "English",
    volume = "16",
    pages = "5480--5492",
    journal = "Molecular Biology of the Cell",
    issn = "1059-1524",
    publisher = "AMERICAN SOCIETY FOR CELL BIOLOGY",

    }

    The oxysterol-binding protein homologue ORP1L interacts with Rab7 and alters functional properties of late endocytic compartments. / Johansson, Marie; Lehto, Markku; Tanhuanpää, Kimmo; Cover, Timothy L; Olkkonen, Vesa M.

    julkaisussa: Molecular Biology of the Cell, Vuosikerta 16, 2005, s. 5480-5492.

    Tutkimustuotos: ArtikkelijulkaisuArtikkeliTieteellinenvertaisarvioitu

    TY - JOUR

    T1 - The oxysterol-binding protein homologue ORP1L interacts with Rab7 and alters functional properties of late endocytic compartments

    AU - Johansson, Marie

    AU - Lehto, Markku

    AU - Tanhuanpää, Kimmo

    AU - Cover, Timothy L

    AU - Olkkonen, Vesa M

    PY - 2005

    Y1 - 2005

    N2 - ORP1L is a member of the human oxysterol-binding protein (OSBP) family. ORP1L localizes to late endosomes (LEs)/lysosomes, colocalizing with the GTPases Rab7 and Rab9 and lysosome-associated membrane protein-1. We demonstrate that ORP1L interacts physically with Rab7, preferentially with its GTP-bound form, and provide evidence that ORP1L stabilizes GTP-bound Rab7 on LEs/lysosomes. The Rab7-binding determinant is mapped to the ankyrin repeat (ANK) region of ORP1L. The pleckstrin homology domain (PHD) of ORP1L binds phosphoinositides with low affinity and specificity. ORP1L, ANK- and ANK+PHD fragments induce perinuclear clustering of LE/lysosomes. This is dependent on an intact microtubule network and a functional dynein/dynactin motor complex. The dominant inhibitory Rab7 mutant T22N reverses the LE clustering, suggesting that the effect is dependent on active Rab7. Transport of fluorescent dextran to LEs is inhibited by overexpression of ORP1L. Overexpression of ORP1L, and in particular the N-terminal fragments of ORP1L, inhibits vacuolation of LE caused by Helicobacter pylori toxin VacA, a process also involving Rab7. The present study demonstrates that ORP1L binds to Rab7, modifies its functional cycle, and can interfere with LE/lysosome organization and endocytic membrane trafficking. This is the first report of a direct connection between the OSBP-related protein family and the Rab GTPases.

    AB - ORP1L is a member of the human oxysterol-binding protein (OSBP) family. ORP1L localizes to late endosomes (LEs)/lysosomes, colocalizing with the GTPases Rab7 and Rab9 and lysosome-associated membrane protein-1. We demonstrate that ORP1L interacts physically with Rab7, preferentially with its GTP-bound form, and provide evidence that ORP1L stabilizes GTP-bound Rab7 on LEs/lysosomes. The Rab7-binding determinant is mapped to the ankyrin repeat (ANK) region of ORP1L. The pleckstrin homology domain (PHD) of ORP1L binds phosphoinositides with low affinity and specificity. ORP1L, ANK- and ANK+PHD fragments induce perinuclear clustering of LE/lysosomes. This is dependent on an intact microtubule network and a functional dynein/dynactin motor complex. The dominant inhibitory Rab7 mutant T22N reverses the LE clustering, suggesting that the effect is dependent on active Rab7. Transport of fluorescent dextran to LEs is inhibited by overexpression of ORP1L. Overexpression of ORP1L, and in particular the N-terminal fragments of ORP1L, inhibits vacuolation of LE caused by Helicobacter pylori toxin VacA, a process also involving Rab7. The present study demonstrates that ORP1L binds to Rab7, modifies its functional cycle, and can interfere with LE/lysosome organization and endocytic membrane trafficking. This is the first report of a direct connection between the OSBP-related protein family and the Rab GTPases.

    U2 - 10.1091/mbc.E05-03-0189

    DO - 10.1091/mbc.E05-03-0189

    M3 - Article

    VL - 16

    SP - 5480

    EP - 5492

    JO - Molecular Biology of the Cell

    JF - Molecular Biology of the Cell

    SN - 1059-1524

    ER -