scholarly journals Identification and evaluation of metastasis-related proteins, oxysterol binding protein-like 5 and calumenin, in lung tumors

2015 ◽  
Vol 47 (1) ◽  
pp. 195-205 ◽  
Author(s):  
KAZUYA NAGANO ◽  
SUNAO IMAI ◽  
XILULI ZHAO ◽  
TAKUYA YAMASHITA ◽  
YASUO YOSHIOKA ◽  
...  
Keyword(s):  
Binding Protein ◽  
Lung Tumors ◽  
Oxysterol Binding Protein ◽  
Related Proteins

scholarly journals A role for oxysterol-binding protein–related protein 5 in endosomal cholesterol trafficking

2011 ◽  
Vol 192 (1) ◽  
pp. 121-135 ◽  
Author(s):  
Ximing Du ◽  
Jaspal Kumar ◽  
Charles Ferguson ◽  
Timothy A. Schulz ◽  
Yan Shan Ong ◽  
...  
Keyword(s):  
Binding Protein ◽  
Lipid Binding ◽  
Cholesterol Trafficking ◽  
Cholesterol Accumulation ◽  
Oxysterol Binding Protein ◽  
Late Endosomes ◽  
Evolutionarily Conserved ◽  
Niemann Pick ◽  
Related Proteins ◽  
Lipid Binding Proteins

Oxysterol-binding protein (OSBP) and its related proteins (ORPs) constitute a large and evolutionarily conserved family of lipid-binding proteins that target organelle membranes to mediate sterol signaling and/or transport. Here we characterize ORP5, a tail-anchored ORP protein that localizes to the endoplasmic reticulum. Knocking down ORP5 causes cholesterol accumulation in late endosomes and lysosomes, which is reminiscent of the cholesterol trafficking defect in Niemann Pick C (NPC) fibroblasts. Cholesterol appears to accumulate in the limiting membranes of endosomal compartments in ORP5-depleted cells, whereas depletion of NPC1 or both ORP5 and NPC1 results in luminal accumulation of cholesterol. Moreover, trans-Golgi resident proteins mislocalize to endosomal compartments upon ORP5 depletion, which depends on a functional NPC1. Our results establish the first link between NPC1 and a cytoplasmic sterol carrier, and suggest that ORP5 may cooperate with NPC1 to mediate the exit of cholesterol from endosomes/lysosomes.

scholarly journals Lipid-regulated sterol transfer between closely apposed membranes by oxysterol-binding protein homologues

2009 ◽  
Vol 187 (6) ◽  
pp. 889-903 ◽  
Author(s):  
Timothy A. Schulz ◽  
Mal-Gi Choi ◽  
Sumana Raychaudhuri ◽  
Jason A. Mears ◽  
Rodolfo Ghirlando ◽  
...  
Keyword(s):  
Binding Protein ◽  
Binding Pocket ◽  
Lipid Binding ◽  
Dependent Manner ◽  
Oxysterol Binding Protein ◽  
The Core ◽  
Contact Sites ◽  
Core Lipid ◽  
Related Proteins ◽  
Distal Site

Sterols are transferred between cellular membranes by vesicular and poorly understood nonvesicular pathways. Oxysterol-binding protein–related proteins (ORPs) have been implicated in sterol sensing and nonvesicular transport. In this study, we show that yeast ORPs use a novel mechanism that allows regulated sterol transfer between closely apposed membranes, such as organelle contact sites. We find that the core lipid-binding domain found in all ORPs can simultaneously bind two membranes. Using Osh4p/Kes1p as a representative ORP, we show that ORPs have at least two membrane-binding surfaces; one near the mouth of the sterol-binding pocket and a distal site that can bind a second membrane. The distal site is required for the protein to function in cells and, remarkably, regulates the rate at which Osh4p extracts and delivers sterols in a phosphoinositide-dependent manner. Together, these findings suggest a new model of how ORPs could sense and regulate the lipid composition of adjacent membranes.

Fungal oxysterol-binding protein-related proteins promote pathogen virulence and activate plant immunity

2021 ◽  
Author(s):  
Meng-Meng Chen ◽  
Si-Ru Yang ◽  
Jian Wang ◽  
Ya-Li Fang ◽  
You-Liang Peng ◽  
...  
Keyword(s):  
Innate Immunity ◽  
Oxidative Burst ◽  
Plant Disease Resistance ◽  
Binding Protein ◽  
Plant Innate Immunity ◽  
Suspension Cells ◽  
Callose Deposition ◽  
Fungal Virulence ◽  
Oxysterol Binding Protein ◽  
Related Proteins

Abstract Oxysterol-binding protein-related proteins (ORPs) are a conserved class of lipid transfer proteins that are closely involved in multiple cellular processes in eukaryotes but their roles in plant-pathogen interactions are mostly unknown. We showed that transient expression of ORPs of Magnaporthe oryzae (MoORPs) in Nicotiana benthamina plants triggered oxidative burst and cell death; treatment of tobacco Bright Yellow-2 suspension cells with recombinant MoORPs elicited the production of reactive oxygen species. Despite that ORPs are normally described as intracellular proteins, we detected MoORPs in fungal cultural filtrates and intercellular fluids from barley plants infected with the fungus. More importantly, infiltration of Arabidopsis plants with recombinant Arabidopsis or fungal ORPs activated oxidative burst, callose deposition, PR1 gene expression, and enhanced plant disease resistance, implying that ORPs may function as endogenous and exogenous danger signals triggering plant innate immunity. Extracellular application of fungal ORPs exerted an opposite impact on salicylic acid and jasmonic acid/ethylene signaling pathways. The Brassinosteroid Insensitive 1-associated Kinase 1 was dispensable for the ORP-activated defense. Besides, simultaneous knockout of MoORP1 and MoORP3 abolished fungal colony radial growth and conidiation, whereas double knockout of MoORP1 and MoORP2 compromised fungal virulence on barley and rice plants. These observations collectively highlight the multifaceted role of MoORPs in the modulation of plant innate immunity and promotion of fungal development and virulence in M. oryzae.

scholarly journals Nonvesicular sterol movement from plasma membrane to ER requires oxysterol-binding protein–related proteins and phosphoinositides

2006 ◽  
Vol 173 (1) ◽  
pp. 107-119 ◽  
Author(s):  
Sumana Raychaudhuri ◽  
Young Jun Im ◽  
James H. Hurley ◽  
William A. Prinz
Keyword(s):  
Plasma Membrane ◽  
Binding Protein ◽  
Large Family ◽  
Lipid Binding ◽  
Oxysterol Binding Protein ◽  
Sterol Transport ◽  
Cellular Compartments ◽  
Related Proteins ◽  
Lipid Binding Proteins

Sterols are moved between cellular membranes by nonvesicular pathways whose functions are poorly understood. In yeast, one such pathway transfers sterols from the plasma membrane (PM) to the endoplasmic reticulum (ER). We show that this transport requires oxysterol-binding protein (OSBP)–related proteins (ORPs), which are a large family of conserved lipid-binding proteins. We demonstrate that a representative member of this family, Osh4p/Kes1p, specifically facilitates the nonvesicular transfer of cholesterol and ergosterol between membranes in vitro. In addition, Osh4p transfers sterols more rapidly between membranes containing phosphoinositides (PIPs), suggesting that PIPs regulate sterol transport by ORPs. We confirmed this by showing that PM to ER sterol transport slows dramatically in mutants with conditional defects in PIP biosynthesis. Our findings argue that ORPs move sterols among cellular compartments and that sterol transport and intracellular distribution are regulated by PIPs.

WITHDRAWN: The Fundamental And Pathological Importance Of Oxysterol Binding Protein And Its Related Proteins

2018 ◽  
pp. jlr.R088682 ◽  
Author(s):  
Danielle E. Dye ◽  
Mark A. Bieniawski ◽  
Sarah C. E. Wright ◽  
Angela McCauley ◽  
Deirdre R. Coombe ◽  
...  
Keyword(s):  
Binding Protein ◽  
Oxysterol Binding Protein ◽  
Related Proteins

scholarly journals The mammalian oxysterol-binding protein-related proteins (ORPs) bind 25-hydroxycholesterol in an evolutionarily conserved pocket

2007 ◽  
Vol 405 (3) ◽  
pp. 473-480 ◽  
Author(s):  
Monika Suchanek ◽  
Riikka Hynynen ◽  
Gerd Wohlfahrt ◽  
Markku Lehto ◽  
Marie Johansson ◽  
...  
Keyword(s):  
Ligand Binding ◽  
Structural Model ◽  
Binding Protein ◽  
Site Directed Mutagenesis ◽  
Pleckstrin Homology Domain ◽  
Ph Domain ◽  
Oxysterol Binding Protein ◽  
Related Proteins ◽  
Sterol Binding

OSBP (oxysterol-binding protein) homologues, ORPs (OSBP-related proteins), constitute a 12-member family in mammals. We employed an in vitro [3H]25OH (25-hydroxycholesterol)-binding assay with purified recombinant proteins as well as live cell photo-cross-linking with [3H]photo-25OH and [3H]photoCH (photo-cholesterol), to investigate sterol binding by the mammalian ORPs. ORP1 and ORP2 [a short ORP consisting of an ORD (OSBP-related ligand-binding domain) only] were in vitro shown to bind 25OH. GST (glutathione S-transferase) fusions of the ORP1L [long variant with an N-terminal extension that carries ankyrin repeats and a PH domain (pleckstrin homology domain)] and ORP1S (short variant consisting of an ORD only) variants bound 25OH with similar affinity (ORP1L, Kd=9.7×10−8 M; ORP1S, Kd=8.4 ×10−8 M), while the affinity of GST–ORP2 for 25OH was lower (Kd=3.9×10−6 M). Molecular modelling suggested that ORP2 has a sterol-binding pocket similar to that of Saccharomyces cerevisiae Osh4p. This was confirmed by site-directed mutagenesis of residues in proximity of the bound sterol in the structural model. Substitution of Ile249 by tryptophan or Lys150 by alanine markedly inhibited 25OH binding by ORP2. In agreement with the in vitro data, ORP1L, ORP1S, and ORP2 were cross-linked with photo-25OH in live COS7 cells. Furthermore, in experiments with either truncated cDNAs encoding the OSBP-related ligand-binding domains of the ORPs or the full-length proteins, photo-25OH was bound to OSBP, ORP3, ORP4, ORP5, ORP6, ORP7, ORP8, ORP10 and ORP11. In addition, the ORP1L variant and ORP3, ORP5, and ORP8 were cross-linked with photoCH. The present study identifies ORP1 and ORP2 as OSBPs and suggests that most of the mammalian ORPs are able to bind sterols.

Functional implications of sterol transport by the oxysterol-binding protein gene family

2010 ◽  
Vol 429 (1) ◽  
pp. 13-24 ◽  
Author(s):  
Mike H. Ngo ◽  
Terry R. Colbourne ◽  
Neale D. Ridgway
Keyword(s):  
Protein Gene ◽  
Binding Protein ◽  
Effector Proteins ◽  
Oxysterol Binding Protein ◽  
Sterol Transport ◽  
Primary Activity ◽  
Functional Implications ◽  
Membrane Compartments ◽  
Binding Protein Gene ◽  
Related Proteins

Cholesterol and its numerous oxygenated derivatives (oxysterols) profoundly affect the biophysical properties of membranes, and positively and negatively regulate sterol homoeostasis through interaction with effector proteins. As the bulk of cellular sterols are segregated from the sensory machinery that controls homoeostatic responses, an important regulatory step involves sterol transport or signalling between membrane compartments. Evidence for rapid, energy-independent transport between organelles has implicated transport proteins, such as the eukaryotic family of OSBP (oxysterol-binding protein)/ORPs (OSBP-related proteins). Since the founding member of this family was identified more than 25 years ago, accumulated evidence has implicated OSBP/ORPs in sterol signalling and/or sterol transport functions. However, recent evidence of sterol transfer activity by OSBP/ORPs suggests that other seemingly disparate functions could be the result of alterations in membrane sterol distribution or ancillary to this primary activity.

scholarly journals Oxysterol-binding protein (OSBP) is required for the perinuclear localization of intra-Golgi v-SNAREs

2013 ◽  
Vol 24 (22) ◽  
pp. 3534-3544 ◽  
Author(s):  
Taki Nishimura ◽  
Yasunori Uchida ◽  
Rieko Yachi ◽  
Tetyana Kudlyk ◽  
Vladimir Lupashin ◽  
...  
Keyword(s):  
Cholesterol Level ◽  
Binding Protein ◽  
Cholesterol Depletion ◽  
Oxysterol Binding Protein ◽  
Golgi Localization ◽  
Protein Receptors ◽  
Intracellular Organelles ◽  
Endoplasmic Reticulum Targeting ◽  
Related Proteins ◽  
Interfering Rna

Oxysterol-binding protein (OSBP) and OSBP-related proteins (ORPs) have been implicated in the distribution of sterols among intracellular organelles. OSBP regulates the Golgi cholesterol level, but how it relates to Golgi function is elusive. Here we report that OSBP is essential for the localization of intra-Golgi soluble vesicle N-ethylmaleimide-sensitive fusion attachment protein receptors (v-SNAREs). Depletion of OSBP by small interfering RNA causes mislocalization of intra-Golgi v-SNAREs GS28 and GS15 throughout the cytoplasm without affecting the perinuclear localization of Golgi target-SNARE syntaxin5 and reduces the abundance of a Golgi enzyme, mannosidase II (Man II). GS28 mislocalization and Man II reduction are also induced by cellular cholesterol depletion. Three domains of OSBP—an endoplasmic reticulum–targeting domain, a Golgi-targeting domain, and a sterol-binding domain—are all required for Golgi localization of GS28. Finally, GS28 mislocalization and Man II reduction in OSBP-depleted cells are largely restored by depletion of ArfGAP1, a regulator of the budding of coat protein complex (COP)-I vesicles. From these results, we postulate that Golgi cholesterol level, which is controlled by OSBP, is essential for Golgi localization of intra-Golgi v-SNAREs by ensuring proper COP-I vesicle transport.

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