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 OSBP-Related Protein Family in Lipid Transport over Membrane Contact Sites

2015 ◽  
Vol 8s1 ◽  
pp. LPI.S31726 ◽  
Author(s):  
Vesa M. Olkkonen
Keyword(s):  
Endoplasmic Reticulum ◽  
Mammalian Cells ◽  
Binding Protein ◽  
High Capacity ◽  
Retrograde Transport ◽  
Protein Family ◽  
Oxysterol Binding Protein ◽  
Membrane Contact Sites ◽  
Contact Sites ◽  
Membrane Contact

Increasing evidence suggests that oxysterol-binding protein-related proteins (ORPs) localize at membrane contact sites, which are high-capacity platforms for inter-organelle exchange of small molecules and information. ORPs can simultaneously associate with the two apposed membranes and transfer lipids across the interbilayer gap. Oxysterol-binding protein moves cholesterol from the endoplasmic reticulum to trans-Golgi, driven by the retrograde transport of phosphatidylinositol-4-phosphate (PI4P). Analogously, yeast Osh6p mediates the transport of phosphatidylserine from the endoplasmic reticulum to the plasma membrane in exchange for PI4P, and ORP5 and -8 are suggested to execute similar functions in mammalian cells. ORPs may share the capacity to bind PI4P within their ligand-binding domain, prompting the hypothesis that bidirectional transport of a phosphoinositide and another lipid may be a common theme among the protein family. This model, however, needs more experimental support and does not exclude a function of ORPs in lipid signaling.

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 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 MLN64 Is Involved in Actin-mediated Dynamics of Late Endocytic Organelles

2005 ◽  
Vol 16 (8) ◽  
pp. 3873-3886 ◽  
Author(s):  
Maarit Hölttä-Vuori ◽  
Fabien Alpy ◽  
Kimmo Tanhuanpää ◽  
Eija Jokitalo ◽  
Aino-Liisa Mutka ◽  
...  
Keyword(s):  
Membrane Protein ◽  
Unknown Function ◽  
Cell Periphery ◽  
Dependent Manner ◽  
Protein Overexpression ◽  
Wild Type ◽  
Functional Connection ◽  
Late Endosomes ◽  
Endosomal Membranes ◽  
Cholesterol Binding

MLN64 is a late endosomal cholesterol-binding membrane protein of an unknown function. Here, we show that MLN64 depletion results in the dispersion of late endocytic organelles to the cell periphery similarly as upon pharmacological actin disruption. The dispersed organelles in MLN64 knockdown cells exhibited decreased association with actin and the Arp2/3 complex subunit p34-Arc. MLN64 depletion was accompanied by impaired fusion of late endocytic organelles and delayed cargo degradation. MLN64 overexpression increased the number of actin and p34-Arc-positive patches on late endosomes, enhanced the fusion of late endocytic organelles in an actin-dependent manner, and stimulated the deposition of sterol in late endosomes harboring the protein. Overexpression of wild-type MLN64 was capable of rescuing the endosome dispersion in MLN64-depleted cells, whereas mutants of MLN64 defective in cholesterol binding were not, suggesting a functional connection between MLN64-mediated sterol transfer and actin-dependent late endosome dynamics. We propose that local sterol enrichment by MLN64 in the late endosomal membranes facilitates their association with actin, thereby governing actin-dependent fusion and degradative activity of late endocytic organelles.

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