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.

journal_name

Mol Biol Cell

authors

Johansson M,Lehto M,Tanhuanpää K,Cover TL,Olkkonen VM

doi

10.1091/mbc.e05-03-0189

keywords:

subject

Has Abstract

pub_date

2005-12-01 00:00:00

pages

5480-92

issue

12

eissn

1059-1524

issn

1939-4586

pii

E05-03-0189

journal_volume

16

pub_type

杂志文章
  • PKC-mediated phosphorylation of nuclear lamins at a single serine residue regulates interphase nuclear size in Xenopus and mammalian cells.

    abstract::How nuclear size is regulated is a fundamental cell-biological question with relevance to cancers, which often exhibit enlarged nuclei. We previously reported that conventional protein kinase C (cPKC) contributes to nuclear size reductions that occur during early Xenopus development. Here we report that PKC-mediated p...

    journal_title:Molecular biology of the cell

    pub_type: 杂志文章

    doi:10.1091/mbc.E16-11-0786

    authors: Edens LJ,Dilsaver MR,Levy DL

    更新日期:2017-05-15 00:00:00

  • The structure of the gamma-tubulin small complex: implications of its architecture and flexibility for microtubule nucleation.

    abstract::The gamma-tubulin small complex (gamma-TuSC) is an evolutionarily conserved heterotetramer essential for microtubule nucleation. We have determined the structure of the Saccharomyces cerevisiae gamma-TuSC at 25-A resolution by electron microscopy. gamma-TuSC is Y-shaped, with an elongated body connected to two arms. G...

    journal_title:Molecular biology of the cell

    pub_type: 杂志文章

    doi:10.1091/mbc.e07-09-0879

    authors: Kollman JM,Zelter A,Muller EG,Fox B,Rice LM,Davis TN,Agard DA

    更新日期:2008-01-01 00:00:00

  • Transition of responsive mechanosensitive elements from focal adhesions to adherens junctions on epithelial differentiation.

    abstract::The skin's epidermis is a multilayered epithelial tissue and the first line of defense against mechanical stress. Its barrier function depends on an integrated assembly and reorganization of cell-matrix and cell-cell junctions in the basal layer and on different intercellular junctions in suprabasal layers. However, h...

    journal_title:Molecular biology of the cell

    pub_type: 杂志文章

    doi:10.1091/mbc.E17-06-0387

    authors: Noethel B,Ramms L,Dreissen G,Hoffmann M,Springer R,Rübsam M,Ziegler WH,Niessen CM,Merkel R,Hoffmann B

    更新日期:2018-09-15 00:00:00

  • Tumor necrosis factor-receptor-associated factor-4 is a positive regulator of transforming growth factor-beta signaling that affects neural crest formation.

    abstract::The transforming growth factor (TGF)-beta superfamily regulates cell proliferation, apoptosis, differentiation, migration, and development. Canonical TGFbeta signals are transduced to the nucleus via Smads in both major signaling branches, bone morphogenetic protein (BMP) or Activin/Nodal/TGFbeta. Smurf ubiquitin (Ub)...

    journal_title:Molecular biology of the cell

    pub_type: 杂志文章

    doi:10.1091/mbc.e08-03-0325

    authors: Kalkan T,Iwasaki Y,Park CY,Thomsen GH

    更新日期:2009-07-01 00:00:00

  • Control of the spindle checkpoint by lateral kinetochore attachment and limited Mad1 recruitment.

    abstract::We observed the dynamic recruitment of spindle checkpoint proteins Mad1 and Bub1 to detached kinetochores in budding yeast using real-time live-cell imaging and quantified recruitment in fixed cells. After induced de novo kinetochore assembly at one pair of sister centromeres, Mad1 appeared after the kinetochore prote...

    journal_title:Molecular biology of the cell

    pub_type: 杂志文章

    doi:10.1091/mbc.E15-05-0276

    authors: Krefman NI,Drubin DG,Barnes G

    更新日期:2015-07-15 00:00:00

  • Translationally repressed mRNA transiently cycles through stress granules during stress.

    abstract::In mammals, repression of translation during stress is associated with the assembly of stress granules in the cytoplasm, which contain a fraction of arrested mRNA and have been proposed to play a role in their storage. Because physical contacts are seen with GW bodies, which contain the mRNA degradation machinery, str...

    journal_title:Molecular biology of the cell

    pub_type: 杂志文章

    doi:10.1091/mbc.e08-05-0499

    authors: Mollet S,Cougot N,Wilczynska A,Dautry F,Kress M,Bertrand E,Weil D

    更新日期:2008-10-01 00:00:00

  • Fibronectin regulates assembly of actin filaments and focal contacts in cultured cells via the heparin-binding site in repeat III13.

    abstract::Fibroblasts, when plated on the extracellular matrix protein fibronectin (FN), rapidly spread and form an organized actin cytoskeleton. This process is known to involve both the central alpha5beta1 integrin-binding and the C-terminal heparin-binding regions of FN. We found that within the heparin-binding region, the i...

    journal_title:Molecular biology of the cell

    pub_type: 杂志文章

    doi:10.1091/mbc.10.5.1521

    authors: Bloom L,Ingham KC,Hynes RO

    更新日期:1999-05-01 00:00:00

  • The desmosome is a mesoscale lipid raft-like membrane domain.

    abstract::Desmogleins (Dsgs) are cadherin family adhesion molecules essential for epidermal integrity. Previous studies have shown that desmogleins associate with lipid rafts, but the significance of this association was not clear. Here, we report that the desmoglein transmembrane domain (TMD) is the primary determinant of raft...

    journal_title:Molecular biology of the cell

    pub_type: 杂志文章

    doi:10.1091/mbc.E18-10-0649

    authors: Lewis JD,Caldara AL,Zimmer SE,Stahley SN,Seybold A,Strong NL,Frangakis AS,Levental I,Wahl JK 3rd,Mattheyses AL,Sasaki T,Nakabayashi K,Hata K,Matsubara Y,Ishida-Yamamoto A,Amagai M,Kubo A,Kowalczyk AP

    更新日期:2019-06-01 00:00:00

  • Autoinhibition of Jak2 tyrosine kinase is dependent on specific regions in its pseudokinase domain.

    abstract::Jak tyrosine kinases have a unique domain structure containing a kinase domain (JH1) adjacent to a catalytically inactive pseudokinase domain (JH2). JH2 is crucial for inhibition of basal Jak activity, but the mechanism of this regulation has remained elusive. We show that JH2 negatively regulated Jak2 in bacterial ce...

    journal_title:Molecular biology of the cell

    pub_type: 杂志文章

    doi:10.1091/mbc.e02-06-0342

    authors: Saharinen P,Vihinen M,Silvennoinen O

    更新日期:2003-04-01 00:00:00

  • Characterization of Mayven, a novel actin-binding protein predominantly expressed in brain.

    abstract::The cytoskeleton plays an important role in neuronal morphogenesis. We have identified and characterized a novel actin-binding protein, termed Mayven, predominantly expressed in brain. Mayven contains a BTB (broad complex, tramtrack, bric-a-brac)/POZ (poxvirus, zinc finger) domain-like structure in the predicted N ter...

    journal_title:Molecular biology of the cell

    pub_type: 杂志文章

    doi:10.1091/mbc.10.7.2361

    authors: Soltysik-Espanola M,Rogers RA,Jiang S,Kim TA,Gaedigk R,White RA,Avraham H,Avraham S

    更新日期:1999-07-01 00:00:00

  • Delineation of the roles played by RasG and RasC in cAMP-dependent signal transduction during the early development of Dictyostelium discoideum.

    abstract::On starvation, the cellular slime mold Dictyostelium discoideum initiates a program of development leading to formation of multicellular structures. The initial cell aggregation requires chemotaxis to cyclic AMP (cAMP) and relay of the cAMP signal by the activation of adenylyl cyclase (ACA), and it has been shown prev...

    journal_title:Molecular biology of the cell

    pub_type: 杂志文章

    doi:10.1091/mbc.e05-11-1019

    authors: Bolourani P,Spiegelman GB,Weeks G

    更新日期:2006-10-01 00:00:00

  • Structure of Shroom domain 2 reveals a three-segmented coiled-coil required for dimerization, Rock binding, and apical constriction.

    abstract::Shroom (Shrm) proteins are essential regulators of cell shape and tissue morpho-logy during animal development that function by interacting directly with the coiled-coil region of Rho kinase (Rock). The Shrm-Rock interaction is sufficient to direct Rock subcellular localization and the subsequent assembly of contracti...

    journal_title:Molecular biology of the cell

    pub_type: 杂志文章

    doi:10.1091/mbc.E11-11-0937

    authors: Mohan S,Rizaldy R,Das D,Bauer RJ,Heroux A,Trakselis MA,Hildebrand JD,VanDemark AP

    更新日期:2012-06-01 00:00:00

  • Mitogen-induced distinct epialleles are phosphorylated at either H3S10 or H3S28, depending on H3K27 acetylation.

    abstract::Stimulation of the MAPK pathway results in mitogen- and stress-activated protein kinase 1/2 (MSK1/2)-catalyzed phosphorylation of histone H3 at serine 10 or 28 and expression of immediate-early (IE) genes. In 10T1/2 mouse fibroblasts, phosphorylation of H3S10 and H3S28 occurs on different H3 molecules and in different...

    journal_title:Molecular biology of the cell

    pub_type: 杂志文章

    doi:10.1091/mbc.E16-08-0618

    authors: Khan DH,Healy S,He S,Lichtensztejn D,Klewes L,Sharma KL,Lau V,Mai S,Delcuve GP,Davie JR

    更新日期:2017-03-15 00:00:00

  • Delineation of the endocytic pathway of substance P and its seven-transmembrane domain NK1 receptor.

    abstract::Many of the actions of the neuropeptide substance P (SP) that are mediated by the neurokinin 1 receptor (NK1-R) desensitize and resensitize, which may be associated with NK1-R endocytosis and recycling. We delineated this endocytic pathway in transfected cells by confocal microscopy using cyanine 3-SP and NK1-R antibo...

    journal_title:Molecular biology of the cell

    pub_type: 杂志文章

    doi:10.1091/mbc.6.5.509

    authors: Grady EF,Garland AM,Gamp PD,Lovett M,Payan DG,Bunnett NW

    更新日期:1995-05-01 00:00:00

  • Atg22 recycles amino acids to link the degradative and recycling functions of autophagy.

    abstract::In response to stress conditions (such as nutrient limitation or accumulation of damaged organelles) and certain pathological situations, eukaryotic cells use autophagy as a survival mechanism. During nutrient stress the main purpose of autophagy is to degrade cytoplasmic materials within the lysosome/vacuole lumen an...

    journal_title:Molecular biology of the cell

    pub_type: 杂志文章

    doi:10.1091/mbc.e06-06-0479

    authors: Yang Z,Huang J,Geng J,Nair U,Klionsky DJ

    更新日期:2006-12-01 00:00:00

  • gp78 functions downstream of Hrd1 to promote degradation of misfolded proteins of the endoplasmic reticulum.

    abstract::Eukaryotic cells eliminate misfolded proteins from the endoplasmic reticulum (ER) via a conserved process termed ER-associated degradation (ERAD). Central regulators of the ERAD system are membrane-bound ubiquitin ligases, which are thought to channel misfolded proteins through the ER membrane during retrotranslocatio...

    journal_title:Molecular biology of the cell

    pub_type: 杂志文章

    doi:10.1091/mbc.E15-06-0354

    authors: Zhang T,Xu Y,Liu Y,Ye Y

    更新日期:2015-12-01 00:00:00

  • Aberrant Caveolin-1-Mediated Smad Signaling and Proliferation Identified by Analysis of Adenine 474 Deletion Mutation (c.474delA) in Patient Fibroblasts: A New Perspective in the Mechanism of Pulmonary Hypertension.

    abstract::A heterozygous Caveolin-1 c.474delA mutation has been identified in a family with heritable pulmonary arterial hypertension (PAH). This frameshift mutation leads to caveolin-1 protein that contains all known functional domains but has a change only in the final 20 amino acids of the C terminus. Here we studied how thi...

    journal_title:Molecular biology of the cell

    pub_type: 杂志文章

    doi:10.1091/mbc.E16-06-0380

    authors: Marsboom G,Chen Z,Yuan Y,Zhang Y,Tiruppathi C,Loyd JE,Austin ED,Machado RF,Minshall RD,Rehman J,Malik AB

    更新日期:2017-03-15 00:00:00

  • GGAs: roles of the different domains and comparison with AP-1 and clathrin.

    abstract::We have previously identified a novel family of proteins called the GGAs (Golgi-localized, gamma-ear-containing, ADP-ribosylation factor-binding proteins). These proteins consist of an NH(2)-terminal VHS domain, followed by a GAT domain, a variable domain, and a gamma-adaptin ear homology domain. Studies from our own ...

    journal_title:Molecular biology of the cell

    pub_type: 杂志文章

    doi:10.1091/mbc.12.11.3573

    authors: Hirst J,Lindsay MR,Robinson MS

    更新日期:2001-11-01 00:00:00

  • 14-3-3 proteins act as negative regulators of the mitotic inducer Cdc25 in Xenopus egg extracts.

    abstract::Cdc25, the dual-specificity phosphatase that dephosphorylates the Cdc2-cyclin B complex at mitosis, is highly regulated during the cell cycle. In Xenopus egg extracts, Cdc25 is associated with two isoforms of the 14-3-3 protein. Cdc25 is complexed primarily with 14-3-3epsilon and to a lesser extent with 14-3-3zeta. Th...

    journal_title:Molecular biology of the cell

    pub_type: 杂志文章

    doi:10.1091/mbc.9.2.345

    authors: Kumagai A,Yakowec PS,Dunphy WG

    更新日期:1998-02-01 00:00:00

  • A novel transcriptional enhancer is involved in the prolactin- and extracellular matrix-dependent regulation of beta-casein gene expression.

    abstract::Lactogenic hormones and extracellular matrix (ECM) act synergistically to regulate beta-casein expression in culture. We have developed a functional subpopulation of the mouse mammary epithelial cell strain COMMA-1D (designated CID 9), which expresses high level of beta-casein, forms alveolar-like structures when plat...

    journal_title:Molecular biology of the cell

    pub_type: 杂志文章

    doi:10.1091/mbc.3.6.699

    authors: Schmidhauser C,Casperson GF,Myers CA,Sanzo KT,Bolten S,Bissell MJ

    更新日期:1992-06-01 00:00:00

  • Tight junction proteins claudin-2 and -12 are critical for vitamin D-dependent Ca2+ absorption between enterocytes.

    abstract::Ca(2+) is absorbed across intestinal epithelial monolayers via transcellular and paracellular pathways, and an active form of vitamin D(3), 1alpha,25-dihydroxyvitamin D(3) [1alpha,25(OH)(2)D(3)], is known to promote intestinal Ca(2+) absorption. However, the molecules driving the paracellular Ca(2+) absorption and its...

    journal_title:Molecular biology of the cell

    pub_type: 杂志文章

    doi:10.1091/mbc.e07-09-0973

    authors: Fujita H,Sugimoto K,Inatomi S,Maeda T,Osanai M,Uchiyama Y,Yamamoto Y,Wada T,Kojima T,Yokozaki H,Yamashita T,Kato S,Sawada N,Chiba H

    更新日期:2008-05-01 00:00:00

  • Oms1 associates with cytochrome c oxidase assembly intermediates to stabilize newly synthesized Cox1.

    abstract::The mitochondrial cytochrome c oxidase assembles in the inner membrane from subunits of dual genetic origin. The assembly process of the enzyme is initiated by membrane insertion of the mitochondria-encoded Cox1 subunit. During complex maturation, transient assembly intermediates, consisting of structural subunits and...

    journal_title:Molecular biology of the cell

    pub_type: 杂志文章

    doi:10.1091/mbc.E15-12-0811

    authors: Bareth B,Nikolov M,Lorenzi I,Hildenbeutel M,Mick DU,Helbig C,Urlaub H,Ott M,Rehling P,Dennerlein S

    更新日期:2016-05-15 00:00:00

  • Role of Akt and c-Jun N-terminal kinase 2 in apoptosis induced by interleukin-4 deprivation.

    abstract::We have shown previously that interleukin-4 (IL-4) protects TS1alphabeta cells from apoptosis, but very little is known about the mechanism by which IL-4 exerts this effect. We found that Akt activity, which is dependent on phosphatidylinositol 3 kinase, is reduced in IL-4-deprived TS1alphabeta cells. Overexpression o...

    journal_title:Molecular biology of the cell

    pub_type: 杂志文章

    doi:10.1091/mbc.9.11.3107

    authors: Cerezo A,Martínez-A C,Lanzarot D,Fischer S,Franke TF,Rebollo A

    更新日期:1998-11-01 00:00:00

  • Rescue of Munc18-1 and -2 double knockdown reveals the essential functions of interaction between Munc18 and closed syntaxin in PC12 cells.

    abstract::Munc18-1 binds to syntaxin-1A via two distinct sites referred to as the "closed" conformation and N terminus binding. The latter has been shown to stimulate soluble N-ethylmaleimide-sensitive factor attachment protein receptor-mediated exocytosis, whereas the former is believed to be inhibitory or dispensable. To prec...

    journal_title:Molecular biology of the cell

    pub_type: 杂志文章

    doi:10.1091/mbc.e09-08-0712

    authors: Han L,Jiang T,Han GA,Malintan NT,Xie L,Wang L,Tse FW,Gaisano HY,Collins BM,Meunier FA,Sugita S

    更新日期:2009-12-01 00:00:00

  • Interactions among Rax1p, Rax2p, Bud8p, and Bud9p in marking cortical sites for bipolar bud-site selection in yeast.

    abstract::In the budding yeast Saccharomyces cerevisiae, selection of the bud site determines the axis of polarized cell growth and eventual oriented cell division. Bud sites are selected in specific patterns depending on cell type. These patterns appear to depend on distinct types of marker proteins in the cell cortex; in part...

    journal_title:Molecular biology of the cell

    pub_type: 杂志文章

    doi:10.1091/mbc.e04-07-0600

    authors: Kang PJ,Angerman E,Nakashima K,Pringle JR,Park HO

    更新日期:2004-11-01 00:00:00

  • Protein kinase activity and identification of a toxic effector domain of the target of rapamycin TOR proteins in yeast.

    abstract::In complex with FKBP12, the immunosuppressant rapamycin binds to and inhibits the yeast TOR1 and TOR2 proteins and the mammalian homologue mTOR/FRAP/RAFT1. The TOR proteins promote cell cycle progression in yeast and human cells by regulating translation and polarization of the actin cytoskeleton. A C-terminal domain ...

    journal_title:Molecular biology of the cell

    pub_type: 杂志文章

    doi:10.1091/mbc.10.8.2531

    authors: Alarcon CM,Heitman J,Cardenas ME

    更新日期:1999-08-01 00:00:00

  • Phosphatidylinositol-(4,5)-bisphosphate regulates clathrin-coated pit initiation, stabilization, and size.

    abstract::Clathrin-mediated endocytosis (CME) is the major mechanism for internalization in mammalian cells. CME initiates by recruitment of adaptors and clathrin to form clathrin-coated pits (CCPs). Nearly half of nascent CCPs abort, whereas others are stabilized by unknown mechanisms and undergo further maturation before pinc...

    journal_title:Molecular biology of the cell

    pub_type: 杂志文章

    doi:10.1091/mbc.E11-04-0362

    authors: Antonescu CN,Aguet F,Danuser G,Schmid SL

    更新日期:2011-07-15 00:00:00

  • Mechanisms of invasion and motility of high-grade gliomas in the brain.

    abstract::High-grade gliomas are especially difficult tumors to treat due to their invasive behavior. This has led to extensive research focusing on arresting glioma cell migration. Cell migration involves the sensing of a migratory cue, followed by polarization in the direction of the cue, and reorganization of the actin cytos...

    journal_title:Molecular biology of the cell

    pub_type: 杂志文章,评审

    doi:10.1091/mbc.E18-02-0123

    authors: Mair DB,Ames HM,Li R

    更新日期:2018-10-15 00:00:00

  • The APC11 RING-H2 finger mediates E2-dependent ubiquitination.

    abstract::Polyubiquitination marks proteins for degradation by the 26S proteasome and is carried out by a cascade of enzymes that includes ubiquitin-activating enzymes (E1s), ubiquitin-conjugating enzymes (E2s), and ubiquitin ligases (E3s). The anaphase-promoting complex or cyclosome (APC/C) comprises a multisubunit ubiquitin l...

    journal_title:Molecular biology of the cell

    pub_type: 杂志文章

    doi:10.1091/mbc.11.7.2315

    authors: Leverson JD,Joazeiro CA,Page AM,Huang Hk,Hieter P,Hunter T

    更新日期:2000-07-01 00:00:00

  • Positive regulation of Wee1 by Chk1 and 14-3-3 proteins.

    abstract::Wee1 inactivates the Cdc2-cyclin B complex during interphase by phosphorylating Cdc2 on Tyr-15. The activity of Wee1 is highly regulated during the cell cycle. In frog egg extracts, it has been established previously that Xenopus Wee1 (Xwee1) is present in a hypophosphorylated, active form during interphase and underg...

    journal_title:Molecular biology of the cell

    pub_type: 杂志文章

    doi:10.1091/mbc.12.3.551

    authors: Lee J,Kumagai A,Dunphy WG

    更新日期:2001-03-01 00:00:00