Home LiteratureArticle Details
PMID: 19564404 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't

Cholesterol sensor ORP1L contacts the ER protein VAP to control Rab7-RILP-p150 Glued and late endosome positioning.

The Journal of cell biology ·Vol. 185 ·No. 7 ·2009-06-29 ·Pages 1209-25

Rocha N, Kuijl C, van der Kant R, Janssen L, Houben D, Janssen H, Zwart W, Neefjes J

Abstract

Late endosomes (LEs) have characteristic intracellular distributions determined by their interactions with various motor proteins. Motor proteins associated to the dynactin subunit p150(Glued) bind to LEs via the Rab7 effector Rab7-interacting lysosomal protein (RILP) in association with the oxysterol-binding protein ORP1L. We found that cholesterol levels in LEs are sensed by ORP1L and are lower in peripheral vesicles. Under low cholesterol conditions, ORP1L conformation induces the formation of endoplasmic reticulum (ER)-LE membrane contact sites. At these sites, the ER protein VAP (VAMP [vesicle-associated membrane protein]-associated ER protein) can interact in trans with the Rab7-RILP complex to remove p150(Glued) and associated motors. LEs then move to the microtubule plus end. Under high cholesterol conditions, as in Niemann-Pick type C disease, this process is prevented, and LEs accumulate at the microtubule minus end as the result of dynein motor activity. These data explain how the ER and cholesterol control the association of LEs with motor proteins and their positioning in cells.

MeSH Terms
Adaptor Proteins, Signal Transducing/genetics,metabolism Androstenes/metabolism Animals Anticholesteremic Agents/metabolism Carrier Proteins/chemistry,genetics,metabolism Cell Line Cholesterol/metabolism Dynactin Complex Endoplasmic Reticulum/metabolism Endosomes/metabolism,ultrastructure Humans Lovastatin/metabolism Microtubule-Associated Proteins/genetics,metabolism Models, Molecular Niemann-Pick Disease, Type C/metabolism Protein Binding Protein Conformation Receptors, Steroid Recombinant Fusion Proteins/genetics,metabolism Vesicular Transport Proteins/genetics,metabolism rab GTP-Binding Proteins/genetics,metabolism rab7 GTP-Binding Proteins
Chemicals
Adaptor Proteins, Signal Transducing Androstenes Anticholesteremic Agents Carrier Proteins DCTN1 protein, human Dynactin Complex Microtubule-Associated Proteins RILP protein, human Receptors, Steroid Recombinant Fusion Proteins VAPA protein, human Vesicular Transport Proteins oxysterol binding protein rab7 GTP-Binding Proteins rab7 GTP-binding proteins, human 3-beta-(2-(diethylamino)ethoxy)androst-5-en-17-one Cholesterol Lovastatin rab GTP-Binding Proteins
Authors & Affiliations
8 authors, click to expand affiliations / ORCID
Rocha Nuno
Division of Cell Biology, The Netherlands Cancer Institute, 1066CX Amsterdam, Netherlands.
Kuijl Coenraad
van der Kant Rik
Janssen Lennert
Houben Diane
Janssen Hans
Zwart Wilbert
Neefjes Jacques
References (58)
58 references, click to expand
  1. Cholesterol level regulates endosome motility via Rab proteins.
    Biophys J. 2008 Feb 15;94(4):1508-20 PMID: 17981910
  2. Cellular cholesterol trafficking and compartmentalization.
    Nat Rev Mol Cell Biol. 2008 Feb;9(2):125-38 PMID: 18216769
  3. Receptor-mediated endocytosis of low-density lipoprotein in cultured cells.
    Methods Enzymol. 1983;98:241-60 PMID: 6321901
  4. Dynactin is required for bidirectional organelle transport.
    J Cell Biol. 2003 Feb 3;160(3):297-301 PMID: 12551954
  5. A conserved ER targeting motif in three families of lipid binding proteins and in Opi1p binds VAP.
    EMBO J. 2003 May 1;22(9):2025-35 PMID: 12727870
  6. A highly conserved binding site in vesicle-associated membrane protein-associated protein (VAP) for the FFAT motif of lipid-binding proteins.
    J Biol Chem. 2005 Apr 8;280(14):14097-104 PMID: 15668246
  7. Monitoring conformational changes of proteins in cells by fluorescence lifetime imaging microscopy.
    Biochem J. 2003 May 15;372(Pt 1):33-40 PMID: 12662152
  8. Type C Niemann-Pick disease: use of hydrophobic amines to study defective cholesterol transport.
    Dev Neurosci. 1991;13(4-5):315-9 PMID: 1817037
  9. Dynein-mediated vesicle transport controls intracellular Salmonella replication.
    Mol Biol Cell. 2004 Jun;15(6):2954-64 PMID: 15064357
  10. Vesicle-associated membrane protein-associated protein-A (VAP-A) interacts with the oxysterol-binding protein to modify export from the endoplasmic reticulum.
    J Biol Chem. 2002 Aug 16;277(33):29908-18 PMID: 12023275
  11. Molecular cloning and characterization of mammalian homologues of vesicle-associated membrane protein-associated (VAMP-associated) proteins.
    Biochem Biophys Res Commun. 1999 Jan 8;254(1):21-6 PMID: 9920726
  12. Human VAP-B is involved in hepatitis C virus replication through interaction with NS5A and NS5B.
    J Virol. 2005 Nov;79(21):13473-82 PMID: 16227268
  13. Spatial separation of HLA-DM/HLA-DR interactions within MIIC and phagosome-induced immune escape.
    Immunity. 2005 Feb;22(2):221-33 PMID: 15723810
  14. Overexpression of the dynamitin (p50) subunit of the dynactin complex disrupts dynein-dependent maintenance of membrane organelle distribution.
    J Cell Biol. 1997 Oct 20;139(2):469-84 PMID: 9334349
  15. The intracellular transport of low density lipoprotein-derived cholesterol is defective in Niemann-Pick type C fibroblasts.
    J Cell Biol. 1989 May;108(5):1625-36 PMID: 2715172
  16. Rab proteins, connecting transport and vesicle fusion.
    Traffic. 2005 Dec;6(12):1070-7 PMID: 16262719
  17. Structural mechanism for sterol sensing and transport by OSBP-related proteins.
    Nature. 2005 Sep 1;437(7055):154-8 PMID: 16136145
  18. Mobilization of late-endosomal cholesterol is inhibited by Rab guanine nucleotide dissociation inhibitor.
    Curr Biol. 2000 Jan 27;10(2):95-8 PMID: 10662671
  19. Point mutation of adenosine triphosphate-binding motif generated rigor kinesin that selectively blocks anterograde lysosome membrane transport.
    J Cell Biol. 1995 Nov;131(4):1039-53 PMID: 7490281
  20. Directional instability of microtubule transport in the presence of kinesin and dynein, two opposite polarity motor proteins.
    J Cell Biol. 1992 Dec;119(6):1589-96 PMID: 1469050
  21. Protein transduction of Rab9 in Niemann-Pick C cells reduces cholesterol storage.
    FASEB J. 2005 Sep;19(11):1558-60 PMID: 15972801
  22. Roles of endogenously synthesized sterols in the endocytic pathway.
    J Biol Chem. 2006 Aug 11;281(32):23191-206 PMID: 16737966
  23. Opposing motor activities of dynein and kinesin determine retention and transport of MHC class II-containing compartments.
    J Cell Sci. 1999 Mar;112 ( Pt 6):785-95 PMID: 10036229
  24. Fast flip-flop of cholesterol and fatty acids in membranes: implications for membrane transport proteins.
    Curr Opin Lipidol. 2003 Jun;14(3):263-71 PMID: 12840657
  25. Lipid traffic: floppy drives and a superhighway.
    Nat Rev Mol Cell Biol. 2005 Mar;6(3):209-20 PMID: 15738987
  26. Genome-wide analysis of human kinases in clathrin- and caveolae/raft-mediated endocytosis.
    Nature. 2005 Jul 7;436(7047):78-86 PMID: 15889048
  27. Rab GTPases: specifying and deciphering organelle identity and function.
    Trends Cell Biol. 2001 Dec;11(12):487-91 PMID: 11719054
  28. Late endosomal cholesterol accumulation leads to impaired intra-endosomal trafficking.
    PLoS One. 2007 Sep 05;2(9):e851 PMID: 17786222
  29. Late endosomal membranes rich in lysobisphosphatidic acid regulate cholesterol transport.
    Nat Cell Biol. 1999 Jun;1(2):113-8 PMID: 10559883
  30. Motor neuron disease-associated mutant vesicle-associated membrane protein-associated protein (VAP) B recruits wild-type VAPs into endoplasmic reticulum-derived tubular aggregates.
    J Neurosci. 2007 Sep 5;27(36):9801-15 PMID: 17804640
  31. Interaction with newly synthesized and retained proteins in the endoplasmic reticulum suggests a chaperone function for human integral membrane protein IP90 (calnexin).
    J Biol Chem. 1993 May 5;268(13):9585-92 PMID: 8486646
  32. Human monocytes and neutrophils store transforming growth factor-alpha in a subpopulation of cytoplasmic granules.
    Blood. 1997 Aug 1;90(3):1255-66 PMID: 9242560
  33. Activation of endosomal dynein motors by stepwise assembly of Rab7-RILP-p150Glued, ORP1L, and the receptor betalll spectrin.
    J Cell Biol. 2007 Feb 12;176(4):459-71 PMID: 17283181
  34. Huntingtin phosphorylation acts as a molecular switch for anterograde/retrograde transport in neurons.
    EMBO J. 2008 Aug 6;27(15):2124-34 PMID: 18615096
  35. Cellular mechanism of U18666A-mediated apoptosis in cultured murine cortical neurons: bridging Niemann-Pick disease type C and Alzheimer's disease.
    Cell Signal. 2006 Nov;18(11):1844-53 PMID: 16797161
  36. Lipid and cholesterol trafficking in NPC.
    Biochim Biophys Acta. 2004 Oct 11;1685(1-3):28-37 PMID: 15465424
  37. Correcting confocal acquisition to optimize imaging of fluorescence resonance energy transfer by sensitized emission.
    Biophys J. 2004 Apr;86(4):2517-29 PMID: 15041688
  38. The Rab7 effector protein RILP controls lysosomal transport by inducing the recruitment of dynein-dynactin motors.
    Curr Biol. 2001 Oct 30;11(21):1680-5 PMID: 11696325
  39. Morphogenesis of the endoplasmic reticulum: beyond active membrane expansion.
    Traffic. 2006 Jun;7(6):639-46 PMID: 16683914
  40. The intracellular transport of low density lipoprotein-derived cholesterol is inhibited in Chinese hamster ovary cells cultured with 3-beta-[2-(diethylamino)ethoxy]androst-5-en-17-one.
    J Biol Chem. 1989 Jul 15;264(20):11796-806 PMID: 2745416
  41. Rab proteins as membrane organizers.
    Nat Rev Mol Cell Biol. 2001 Feb;2(2):107-17 PMID: 11252952
  42. Biochemical characterization and cellular localization of a formalin-resistant melanoma-associated antigen reacting with monoclonal antibody NKI/C-3.
    Int J Cancer. 1985 Mar 15;35(3):287-95 PMID: 3882581
  43. Lysed chromatophores: a model system for the study of bidirectional organelle transport.
    Methods Cell Biol. 1989;31:3-24 PMID: 2779450
  44. The major substrates for TAP in vivo are derived from newly synthesized proteins.
    Nature. 2000 Apr 13;404(6779):774-8 PMID: 10783892
  45. Late endosome motility depends on lipids via the small GTPase Rab7.
    EMBO J. 2002 Mar 15;21(6):1289-300 PMID: 11889035
  46. Kinesin-2 is a motor for late endosomes and lysosomes.
    Traffic. 2005 Dec;6(12):1114-24 PMID: 16262723
  47. Simultaneous detection of multiple green fluorescent proteins in live cells by fluorescence lifetime imaging microscopy.
    Curr Biol. 1999 Mar 11;9(5):269-72 PMID: 10074454
  48. Evidence for a cholesterol transport pathway from lysosomes to endoplasmic reticulum that is independent of the plasma membrane.
    J Biol Chem. 1998 Feb 13;273(7):4266-74 PMID: 9461625
  49. Signal-dependent membrane targeting by pleckstrin homology (PH) domains.
    Biochem J. 2000 Aug 15;350 Pt 1:1-18 PMID: 10926821
  50. Modulation of receptor recycling and degradation by the endosomal kinesin KIF16B.
    Cell. 2005 May 6;121(3):437-50 PMID: 15882625
  51. Radial extension of macrophage tubular lysosomes supported by kinesin.
    Nature. 1990 Aug 30;346(6287):864-6 PMID: 1697403
  52. The mammalian oxysterol-binding protein-related proteins (ORPs) bind 25-hydroxycholesterol in an evolutionarily conserved pocket.
    Biochem J. 2007 Aug 1;405(3):473-80 PMID: 17428193
  53. Interaction of a Golgi-associated kinesin-like protein with Rab6.
    Science. 1998 Jan 23;279(5350):580-5 PMID: 9438855
  54. The oxysterol-binding protein homologue ORP1L interacts with Rab7 and alters functional properties of late endocytic compartments.
    Mol Biol Cell. 2005 Dec;16(12):5480-92 PMID: 16176980
  55. Niemann-Pick C1 disease gene: homology to mediators of cholesterol homeostasis.
    Science. 1997 Jul 11;277(5323):228-31 PMID: 9211849
  56. The ABCA1 transporter modulates late endocytic trafficking: insights from the correction of the genetic defect in Tangier disease.
    J Biol Chem. 2004 Apr 9;279(15):15571-8 PMID: 14747463
  57. Role of cholesterol and lipid organization in disease.
    Nature. 2005 Dec 1;438(7068):612-21 PMID: 16319881
  58. Fluorescence lifetime imaging microscopy: spatial resolution of biochemical processes in the cell.
    Trends Cell Biol. 1999 Feb;9(2):48-52 PMID: 10087617
Article Info
Journal
The Journal of cell biology
Abbr.
J Cell Biol
ISSN
1540-8140
DOI
10.1083/jcb.200811005
Published
2009-06-29
Pages
1209-25
Language
English
Region
United States
NLM ID
0375356
PMCID
PMC2712958
Subset
IM
External Links
PubMed source DOI: 10.1083/jcb.200811005 PMC Full Text View journal details
Analysis Services
Analysis Services

Contact

No. 2 Wenbo Road, Zhangqiu District, Jinan, Shandong

Qilu Normal University · Genelibs Bioinformatics Lab

750 Shunhua Rd, Jinan

2F, Bldg F, University Science Park

Tel: 0531-88819269

WeChat Official Account

Follow our WeChat subscription account for real-time updates and the latest in medical and biological research.


Business Email

E-mail: [email protected]

Copyright © 2026.Genelibs Jinan Honghui Biotechnology Co., Ltd. 鲁ICP备20007159号-2