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.

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 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 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 Regulation of Oxysterol-binding Protein Golgi Localization through Protein Kinase D–mediated Phosphorylation

2010 ◽  
Vol 21 (13) ◽  
pp. 2327-2337 ◽  
Author(s):  
Sokha Nhek ◽  
Mike Ngo ◽  
Xuemei Yang ◽  
Michelle M. Ng ◽  
Seth J. Field ◽  
...  
Keyword(s):  
Plasma Membrane ◽  
Protein Kinase ◽  
Binding Protein ◽  
Critical Role ◽  
Protein Kinase D ◽  
Cholesterol Depletion ◽  
Oxysterol Binding Protein ◽  
Golgi Localization ◽  
Golgi Network

Protein kinase D (PKD) plays a critical role at the trans-Golgi network by regulating the fission of transport carriers destined for the plasma membrane. Two known Golgi-localized PKD substrates, PI4-kinase IIIβ and the ceramide transfer protein CERT, mediate PKD signaling to influence vesicle trafficking to the plasma membrane and sphingomyelin synthesis, respectively. PKD is recruited and activated at the Golgi through interaction with diacylglycerol, a pool of which is generated as a by-product of sphingomyelin synthesis from ceramide. Here we identify a novel substrate of PKD at the Golgi, the oxysterol-binding protein OSBP. Using a substrate-directed phospho-specific antibody that recognizes the optimal PKD consensus motif, we show that PKD phosphorylates OSBP at Ser240 in vitro and in cells. We further show that OSBP phosphorylation occurs at the Golgi. Phosphorylation of OSBP by PKD does not modulate dimerization, sterol binding, or affinity for PI(4)P. Instead, phosphorylation attenuates OSBP Golgi localization in response to 25-hydroxycholesterol and cholesterol depletion, impairs CERT Golgi localization, and promotes Golgi fragmentation.

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 The activities of LDL Receptor-related Protein-1 (LRP1) compartmentalize into distinct plasma membrane microdomains

2016 ◽  
Vol 76 ◽  
pp. 42-51 ◽  
Author(s):  
Emilia Laudati ◽  
Andrew S. Gilder ◽  
Michael S. Lam ◽  
Roberta Misasi ◽  
Maurizio Sorice ◽  
...  
Keyword(s):  
Plasma Membrane ◽  
Ldl Receptor ◽  
Membrane Microdomains ◽  
Related Protein ◽  
Plasma Membrane Microdomains

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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