scholarly journals The Two Variants of Oxysterol Binding Protein-related Protein-1 Display Different Tissue Expression Patterns, Have Different Intracellular Localization, and Are Functionally Distinct

2003 ◽  
Vol 14 (3) ◽  
pp. 903-915 ◽  
Author(s):  
Marie Johansson ◽  
Virginie Bocher ◽  
Markku Lehto ◽  
Giulia Chinetti ◽  
Esa Kuismanen ◽  
...  
Keyword(s):  
Binding Protein ◽  
Expression Patterns ◽  
Intracellular Localization ◽  
Tissue Expression ◽  
Ankyrin Repeat ◽  
Pleckstrin Homology Domain ◽  
Related Protein ◽  
Amino Terminal ◽  
Oxysterol Binding Protein ◽  
Late Endosomes

Oxysterol binding protein (OSBP) homologs comprise a family of 12 proteins in humans ( Jaworski et al., 2001 ; Lehtoet al., 2001 ). Two variants of OSBP-related protein (ORP) 1 have been identified: a short one that consists of the carboxy-terminal ligand binding domain only (ORP1S, 437 aa) and a longer N-terminally extended form (ORP1L, 950 aa) encompassing three ankyrin repeats and a pleckstrin homology domain (PHD). We now report that the two mRNAs show marked differences in tissue expression. ORP1S predominates in skeletal muscle and heart, whereas ORP1L is the most abundant form in brain and lung. On differentiation of primary human monocytes into macrophages, both ORP1S and ORP1L mRNAs were induced, the up-regulation of ORP1L being >100-fold. The intracellular localization of the two ORP1 variants was found to be different. Whereas ORP1S is largely cytosolic, the ORP1L variant localizes to late endosomes. A significant amount of ORP1S but only little ORP1L was found in the nucleus. The ORP1L ankyrin repeat region (aa 1–237) was found to localize to late endosomes such as the full-length protein. This localization was even more pronounced for a fragment that additionally includes the PHD (aa 1–408). The amino-terminal region of ORP1L consisting of the ankyrin repeat and PHDs is therefore likely to be responsible for the targeting of ORP1L to late endosomes. Interestingly, overexpression of ORP1L was found to enhance the LXRα-mediated transactivation of a reporter gene, whereas ORP1S failed to influence this process. The results suggest that the two forms of ORP1 are functionally distinct and that ORP1L is involved in control of cellular lipid metabolism.

scholarly journals The Oxysterol-binding Protein Homologue ORP1L Interacts with Rab7 and Alters Functional Properties of Late Endocytic Compartments

2005 ◽  
Vol 16 (12) ◽  
pp. 5480-5492 ◽  
Author(s):  
Marie Johansson ◽  
Markku Lehto ◽  
Kimmo Tanhuanpää ◽  
Timothy L. Cover ◽  
Vesa M. Olkkonen
Keyword(s):  
Membrane Trafficking ◽  
Binding Protein ◽  
Pleckstrin Homology Domain ◽  
Rab Gtpases ◽  
Microtubule Network ◽  
Oxysterol Binding Protein ◽  
Motor Complex ◽  
Late Endosomes ◽  
Endocytic Compartments ◽  
Fluorescent Dextran

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.

ER–endosome contact sites in endosome positioning and protrusion outgrowth

2016 ◽  
Vol 44 (2) ◽  
pp. 441-446 ◽  
Author(s):  
Camilla Raiborg ◽  
Eva M. Wenzel ◽  
Nina M. Pedersen ◽  
Harald Stenmark
Keyword(s):  
Endoplasmic Reticulum ◽  
Binding Protein ◽  
Cell Periphery ◽  
Related Protein ◽  
Gear Shift ◽  
Oxysterol Binding Protein ◽  
Contact Sites ◽  
Late Endosomes ◽  
Microtubule Motor ◽  
Cholesterol Binding

The endoplasmic reticulum (ER) makes abundant contacts with endosomes, and the numbers of contact sites increase as endosomes mature. It is already clear that such contact sites have diverse compositions and functions, but in this mini-review we will focus on two particular types of ER–endosome contact sites that regulate endosome positioning. Formation of ER–endosome contact sites that contain the cholesterol-binding protein oxysterol-binding protein-related protein 1L (ORP1L) is coordinated with loss of the minus-end-directed microtubule motor Dynein from endosomes. Conversely, formation of ER–endosome contact sites that contain the Kinesin-1-binding protein Protrudin results in transfer of the plus-end-directed microtubule motor Kinesin-1 from ER to endosomes. We discuss the possibility that formation of these two types of contact sites is coordinated as a ‘gear-shift’ mechanism for endosome motility, and we review evidence that Kinesin-1-mediated motility of late endosomes (LEs) to the cell periphery promotes outgrowth of neurites and other protrusions.

scholarly journals Oxysterol-binding protein-related protein 1 variants have opposing cholesterol transport activities from the endolysosomes

2020 ◽  
Vol 31 (8) ◽  
pp. 793-802 ◽  
Author(s):  
Kexin Zhao ◽  
Jason Foster ◽  
Neale D. Ridgway
Keyword(s):  
Plasma Membrane ◽  
Cholesterol Efflux ◽  
Binding Protein ◽  
Ldl Receptor ◽  
Full Length ◽  
Receptor Activity ◽  
Cholesterol Transport ◽  
Related Protein ◽  
Oxysterol Binding Protein ◽  
Late Endosomes

OSBPL1 encodes the full-length ORP1L and the truncated variant ORP1S. ORP1S is responsible for transferring cholesterol from late endosomes to the plasma membrane to regulate cholesterol efflux by ABCA1 and LDL receptor activity. ORP1L and ORP1S combine to transport cholesterol from late endosomes to the ER and PM, respectively.

scholarly journals VAMP-associated protein-A and oxysterol-binding protein–related protein 3 promote the entry of late endosomes into the nucleoplasmic reticulum

2018 ◽  
Vol 293 (36) ◽  
pp. 13834-13848 ◽  
Author(s):  
Mark F. Santos ◽  
Germana Rappa ◽  
Jana Karbanová ◽  
Thomas Kurth ◽  
Denis Corbeil ◽  
...  
Keyword(s):  
Binding Protein ◽  
Protein A ◽  
Related Protein ◽  
Oxysterol Binding Protein ◽  
Late Endosomes ◽  
Nucleoplasmic Reticulum

scholarly journals Bis(monoacylglycero)phosphate regulates oxysterol binding protein-related protein 11 dependent sterol trafficking

2019 ◽  
Vol 1864 (9) ◽  
pp. 1247-1257 ◽  
Author(s):  
Maud Arnal-Levron ◽  
Yinan Chen ◽  
Peter Greimel ◽  
Federica Calevro ◽  
Karen Gaget ◽  
...  
Keyword(s):  
Binding Protein ◽  
Related Protein ◽  
Oxysterol Binding Protein ◽  
Sterol Trafficking

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 Oxysterol binding protein-related protein-5 is related to invasion and poor prognosis in pancreatic cancer

2008 ◽  
Vol 99 (12) ◽  
pp. 2387-2394 ◽  
Author(s):  
Yoshikatsu Koga ◽  
Shinji Ishikawa ◽  
Tadahiko Nakamura ◽  
Toshiro Masuda ◽  
Yohei Nagai ◽  
...  
Keyword(s):  
Pancreatic Cancer ◽  
Poor Prognosis ◽  
Binding Protein ◽  
Related Protein ◽  
Oxysterol Binding Protein
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