Cellular and Molecular Life Sciences

, Volume 75, Issue 17, pp 3079–3098 | Cite as

Bridging the molecular and biological functions of the oxysterol-binding protein family

  • Antonietta Pietrangelo
  • Neale D. RidgwayEmail author


Oxysterol-binding protein (OSBP) and OSBP-related proteins (ORPs) constitute a large eukaryotic gene family that transports and regulates the metabolism of sterols and phospholipids. The original classification of the family based on oxysterol-binding activity belies the complex dual lipid-binding specificity of the conserved OSBP homology domain (OHD). Additional protein- and membrane-interacting modules mediate the targeting of select OSBP/ORPs to membrane contact sites between organelles, thus positioning the OHD between opposing membranes for lipid transfer and metabolic regulation. This unique subcellular location, coupled with diverse ligand preferences and tissue distribution, has identified OSBP/ORPs as key arbiters of membrane composition and function. Here, we will review how molecular models of OSBP/ORP-mediated intracellular lipid transport and regulation at membrane contact sites relate to their emerging roles in cellular and organismal functions.


Oxysterol-binding proteins Membrane contact sites Intracellular lipid transport Cancer Dyslipidemia Metabolism Viral replication 



Amyotrophic lateral sclerosis


ATP binding cassette


Carriers of the trans-Golgi network to the cell surface


Ceramide transfer protein


Endoplasmic reticulum


Two phenylalanines in an acidic tract


High density lipoprotein




Hepatocellular carcinoma


Hepatitis C virus


Low density lipoprotein


Late endosomes–lysosomes


Lipid droplet


Liver receptor homolog-1


Liver X receptor


Lipid transfer protein


Membrane contact site


Mammalian target of rapamycin


Niemann–Pick type C


Oxysterol-binding protein


OSBP-related protein


OSBP homology domain


Oxysterol-binding protein homolog


Plasma membrane






Phosphatidylinositol 4-phosphate


Phosphatidylinositol phosphates


Phospholipase C




Rab7-interacting lysosomal protein




Single nucleotide polymorphisms


Sterol regulatory element binding protein


Trans-Golgi network


Vesicle-associated membrane protein-associated protein


  1. 1.
    Holthuis J, Menon AK (2014) Lipid landscapes and pipelines in membrane homeostasis. Nature 510:48–57PubMedCrossRefGoogle Scholar
  2. 2.
    Wong LH, Čopič A, Levine TP (2017) Advances on the transfer of lipids by lipid transfer proteins. Trends Biochem Sci 42:516–530PubMedCrossRefPubMedCentralGoogle Scholar
  3. 3.
    Taylor FR, Kandutsch AA (1985) Oxysterol binding protein. Chem Phys Lipids 38:187–194PubMedCrossRefGoogle Scholar
  4. 4.
    Brown MS, Dana SE, Goldstein JL (1975) Cholesterol ester formation in cultured human fibroblasts. Stimulation by oxygenated sterols. J Biol Chem 250:4025–4027PubMedGoogle Scholar
  5. 5.
    Dawson PA, Ridgway ND, Slaughter CA, Brown MS, Goldstein JL (1989) cDNA cloning and expression of oxysterol-binding protein, an oligomer with a potential leucine zipper. J Biol Chem 264:16798–16803PubMedGoogle Scholar
  6. 6.
    Ridgway ND, Dawson PA, Ho YK, Brown MS, Goldstein JL (1992) Translocation of oxysterol binding protein to Golgi apparatus triggered by ligand binding. J Cell Biol 116:307–319PubMedCrossRefGoogle Scholar
  7. 7.
    Laitinen S, Olkkonen VM, Ehnholm C, Ikonen E (1999) Family of human oxysterol binding protein (OSBP) homologues. A novel member implicated in brain sterol metabolism. J Lipid Res 40:2204–2211PubMedGoogle Scholar
  8. 8.
    Jaworski CJ, Moreira E, Li A, Lee R, Rodriguez IR (2001) A family of 12 human genes containing oxysterol-binding domains. Genomics 78:185–196PubMedCrossRefGoogle Scholar
  9. 9.
    Schulz TA, Prinz WA (2007) Sterol transport in yeast and the oxysterol binding protein homologue (OSH) family. BBA Mol Cell Biol Lipids 1771:769–780CrossRefGoogle Scholar
  10. 10.
    Beh CT, Cool L, Phillips J, Rine J (2001) Overlapping functions of the yeast oxysterol-binding protein homologues. Genetics 157:1117–1140PubMedPubMedCentralGoogle Scholar
  11. 11.
    Kobuna H, Inoue T, Shibata M, Gengyo-Ando K, Yamamoto A, Mitani S, Arai H (2010) Multivesicular body formation requires OSBP-related proteins and cholesterol. PLoS Genet 6:e1001055PubMedCrossRefPubMedCentralGoogle Scholar
  12. 12.
    Ma Z, Liu Z, Huang X (2010) OSBP- and FAN-mediated sterol requirement for spermatogenesis in Drosophila. Development 137:3775–3784PubMedCrossRefGoogle Scholar
  13. 13.
    Ma Z, Liu Z, Huang X (2012) Membrane phospholipid asymmetry counters the adverse effects of sterol overloading in the Golgi membrane of Drosophila. Genetics 190:1299–1308PubMedCrossRefPubMedCentralGoogle Scholar
  14. 14.
    Im Y, Raychaudhuri S, Prinz WA, Hurley JH (2005) Structural mechanism for sterol sensing and transport by OSBP-related proteins. Nature 437:154–158PubMedCrossRefPubMedCentralGoogle Scholar
  15. 15.
    Tong J, Manik MK, Yang H, Im YJ (2016) Structural insights into nonvesicular lipid transport by the oxysterol binding protein homologue family. Biochim Biophys Acta 1861:928–939PubMedCrossRefGoogle Scholar
  16. 16.
    de Saint-Jean M, Delfosse V, Douguet D, Chicanne G, Payrastre B, Bourguet W, Antonny B, Drin G (2011) Osh4p exchanges sterols for phosphatidylinositol 4-phosphate between lipid bilayers. J Cell Biol 195:965–978PubMedCrossRefPubMedCentralGoogle Scholar
  17. 17.
    Tong J, Yang H, Yang H, Eom SH, Im YJ (2013) Structure of Osh3 reveals a conserved mode of phosphoinositide binding in oxysterol-binding proteins. Structure 21:1203–1213PubMedCrossRefGoogle Scholar
  18. 18.
    Manik MK, Yang H, Tong J, Im YJ (2017) Structure of yeast OSBP-related protein Osh1 reveals key determinants for lipid transport and protein targeting at the nucleus-vacuole junction. Structure 25:617–629000PubMedCrossRefGoogle Scholar
  19. 19.
    Kentala H, Weber-Boyvat M, Olkkonen VM (2016) OSBP-related protein family: mediators of lipid transport and signaling at membrane contact sites. Int Rev Cell Mol Biol 321:299–340PubMedCrossRefGoogle Scholar
  20. 20.
    Guo S, Stolz LE, Lemrow SM, York JD (1999) SAC1-like domains of yeast SAC1, INP52, and INP53 and of human synaptojanin encode polyphosphoinositide phosphatases. J Biol Chem 274:12990–12995PubMedCrossRefGoogle Scholar
  21. 21.
    Fang M, Kearns BG, Gedvilaite A, Kagiwada S, Kearns M, Fung MK, Bankaitis VA (1996) Kes1p shares homology with human oxysterol binding protein and participates in a novel regulatory pathway for yeast Golgi-derived transport vesicle biogenesis. EMBO J 15:6447–6459PubMedCrossRefPubMedCentralGoogle Scholar
  22. 22.
    Lagace TA, Byers DM, Cook HW, Ridgway ND (1997) Altered regulation of cholesterol and cholesteryl ester synthesis in Chinese-hamster ovary cells overexpressing the oxysterol-binding protein is dependent on the pleckstrin homology domain. Biochem J 326(Pt 1):205–213PubMedCrossRefPubMedCentralGoogle Scholar
  23. 23.
    Wyles JP, McMaster CR, Ridgway ND (2002) 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 277:29908–29918PubMedCrossRefGoogle Scholar
  24. 24.
    Peretti D, Dahan N, Shimoni E, Hirschberg K, Lev S (2008) Coordinated lipid transfer between the endoplasmic reticulum and the Golgi complex requires the VAP proteins and is essential for Golgi-mediated transport. Mol Biol Cell 19:3871–3884PubMedCrossRefPubMedCentralGoogle Scholar
  25. 25.
    Mesmin B, Bigay J, Moser von Filseck J, Lacas-Gervais S, Drin G, Antonny B (2013) A four-step cycle driven by PI(4)P hydrolysis directs sterol/PI(4)P exchange by the ER–Golgi Tether OSBP. Cell 155:830–843PubMedCrossRefGoogle Scholar
  26. 26.
    Banerji S, Ngo M, Lane CF, Robinson C-A, Minogue S, Ridgway ND (2010) Oxysterol binding protein-dependent activation of sphingomyelin synthesis in the Golgi apparatus requires phosphatidylinositol 4-kinase IIα. Mol Biol Cell 21:4141–4150PubMedCrossRefPubMedCentralGoogle Scholar
  27. 27.
    Perry RJ, Ridgway ND (2006) Oxysterol-binding protein and vesicle-associated membrane protein–associated protein are required for sterol-dependent activation of the ceramide transport protein. Mol Biol Cell 17:2604–2616PubMedCrossRefPubMedCentralGoogle Scholar
  28. 28.
    Slotte PJ (2013) Biological functions of sphingomyelins. Prog Lipid Res 52:424–437PubMedCrossRefGoogle Scholar
  29. 29.
    Wakana Y, Kotake R, Oyama N, Murate M, Kobayashi T, Arasaki K, Inoue H, Tagaya M (2015) CARTS biogenesis requires VAP–lipid transfer protein complexes functioning at the endoplasmic reticulum–Golgi interface. Mol Biol Cell 26:4686–4699PubMedCrossRefPubMedCentralGoogle Scholar
  30. 30.
    Maxfield FR, Wüstner D (2002) Intracellular cholesterol transport. J Clin Investig 110:891–898PubMedCrossRefGoogle Scholar
  31. 31.
    Burgett AW, Poulsen TB, Wangkanont K, Anderson DR, Kikuchi C, Shimada K, Okubo S, Fortner KC, Mimaki Y, Kuroda M, Murphy JP, Schwalb DJ, Petrella EC, Cornella-Taracido I, Schirle M, Tallarico JA, Shair MD (2011) Natural products reveal cancer cell dependence on oxysterol-binding proteins. Nat Chem Biol 7:639–647PubMedCrossRefPubMedCentralGoogle Scholar
  32. 32.
    Mesmin B, Bigay J, Polidori J, Jamecna D, Lacas-Gervais S, Antonny B (2017) Sterol transfer, PI4P consumption, and control of membrane lipid order by endogenous OSBP. EMBO J 36:3156–3174PubMedCrossRefGoogle Scholar
  33. 33.
    Nishimura T, Uchida Y, Yachi R, Kudlyk T, Lupashin V, Inoue T, Taguchi T, Arai H (2013) Oxysterol-binding protein (OSBP) is required for the perinuclear localization of intra-Golgi v-SNAREs. Mol Biol Cell 24:3534–3544PubMedCrossRefPubMedCentralGoogle Scholar
  34. 34.
    Dong R, Saheki Y, Swarup S, Lucast L, Harper JW, De Camilli P (2016) Endosome-ER contacts control actin nucleation and retromer function through VAP-dependent regulation of PI4P. Cell 166:408–423PubMedCrossRefPubMedCentralGoogle Scholar
  35. 35.
    Nishimura T, Inoue T, Shibata N, Sekine A, Takabe W, Noguchi N, Arai H (2005) Inhibition of cholesterol biosynthesis by 25-hydroxycholesterol is independent of OSBP. Genes Cells 10:793–801PubMedCrossRefGoogle Scholar
  36. 36.
    Ghai R, Du X, Wang H, Dong J, Ferguson C, Brown AJ, Parton RG, Wu J-WW, Yang H (2017) ORP5 and ORP8 bind phosphatidylinositol-4, 5-biphosphate (PtdIns(4,5)P 2) and regulate its level at the plasma membrane. Nat Commun 8:757PubMedCrossRefPubMedCentralGoogle Scholar
  37. 37.
    Galmes R, Houcine A, Vliet AR, Agostinis P, Jackson CL, Giordano F (2016) ORP5/ORP8 localize to endoplasmic reticulum–mitochondria contacts and are involved in mitochondrial function. EMBO Rep 17:800–810PubMedCrossRefPubMedCentralGoogle Scholar
  38. 38.
    Steenbergen R, Nanowski TS, Beigneux A, Kulinski A, Young SG, Vance JE (2005) Disruption of the phosphatidylserine decarboxylase gene in mice causes embryonic lethality and mitochondrial defects. J Biol Chem 280:40032–40040PubMedCrossRefPubMedCentralGoogle Scholar
  39. 39.
    Du X, Kumar J, Ferguson C, Schulz TA, Ong YS, Hong W, Prinz WA, Parton RG, Brown AJ, Yang H (2011) A role for oxysterol-binding protein-related protein 5 in endosomal cholesterol trafficking. J Cell Biol 192:121–135PubMedCrossRefPubMedCentralGoogle Scholar
  40. 40.
    Suchanek M, Hynynen R, Wohlfahrt G, Lehto M, Johansson M, Saarinen H, Radzikowska A, Thiele C, Olkkonen VM (2007) The mammalian oxysterol-binding protein-related proteins (ORPs) bind 25-hydroxycholesterol in an evolutionarily conserved pocket. Biochem J. 405:473–480PubMedCrossRefPubMedCentralGoogle Scholar
  41. 41.
    Du X, Zadoorian A, Lukmantara IE, Qi Y, Brown AJ, Yang H (2018) Oxysterol-binding protein-related protein 5 (ORP5) promotes cell proliferation by activation of mTORC1 signaling. J Biol Chem. CrossRefPubMedPubMedCentralGoogle Scholar
  42. 42.
    Xu J, Dang Y, Ren YR, Liu JO (2010) Cholesterol trafficking is required for mTOR activation in endothelial cells. Proc Natl Acad Sci USA 107:4764–4769PubMedCrossRefGoogle Scholar
  43. 43.
    Ikonen E (2008) Cellular cholesterol trafficking and compartmentalization. Nat Rev Mol Cell Biol 9:125–138PubMedCrossRefGoogle Scholar
  44. 44.
    Möbius W, van Donselaar E, Ohno-Iwashita Y, Shimada Y, Heijnen HFG, Slot JW, Geuze HJ (2003) Recycling compartments and the internal vesicles of multivesicular bodies harbor most of the cholesterol found in the endocytic pathway. Traffic 4:222–231PubMedCrossRefGoogle Scholar
  45. 45.
    Vance JE, Karten B (2014) Niemann–Pick C disease and mobilization of lysosomal cholesterol by cyclodextrin. J Lipid Res 55:1609–1621PubMedCrossRefPubMedCentralGoogle Scholar
  46. 46.
    Eden ER, Sanchez-Heras E, Tsapara A, Sobota A, Levine TP, Futter CE (2016) Annexin A1 tethers membrane contact sites that mediate er to endosome cholesterol transport. Dev Cell 37:473–483PubMedCrossRefPubMedCentralGoogle Scholar
  47. 47.
    Friedman JR, DiBenedetto JR, West M, Rowland AA, Voeltz GK (2013) Endoplasmic reticulum–endosome contact increases as endosomes traffic and mature. Mol Biol Cell 24:1030–1040PubMedCrossRefPubMedCentralGoogle Scholar
  48. 48.
    Lehto M, Laitinen S, Chinetti G, Johansson M, Ehnholm C, Staels B, Ikonen E, Olkkonen VM (2001) The OSBP-related protein family in humans. J Lipid Res 42:1203–1213PubMedGoogle Scholar
  49. 49.
    Ouimet M, Hennessy EJ, van Solingen C, Koelwyn GJ, Hussein MA, Ramkhelawon B, Rayner KJ, Temel RE, Perisic L, Hedin U, Maegdefessel L, Garabedian MJ, Holdt LM, Teupser D, Moore KJ (2016) miRNA targeting of oxysterol-binding protein-like 6 regulates cholesterol trafficking and efflux. Arterioscler Thromb Vasc Biol 36:942–951PubMedCrossRefPubMedCentralGoogle Scholar
  50. 50.
    Johansson M, Bocher V, Lehto M, Chinetti G, Kuismanen E, Ehnholm C, Staels B, Olkkonen VM (2003) The two variants of oxysterol binding protein-related protein-1 display different tissue expression patterns, have different intracellular localization, and are functionally distinct. Mol Biol Cell 14:903–915PubMedCrossRefPubMedCentralGoogle Scholar
  51. 51.
    Lee S, Wang P-Y, Jeong Y, Mangelsdorf DJ, Anderson R, Michaely P (2012) Sterol-dependent nuclear import of ORP1S promotes LXR regulated trans-activation of apoE. Exp Cell Res 318:2128–2142PubMedCrossRefGoogle Scholar
  52. 52.
    Johansson M, Olkkonen VM (2005) Assays for interaction between Rab7 and Oxysterol Binding Protein Related Protein 1L (ORP1L). Methods Enzymol 403:743–758PubMedCrossRefGoogle Scholar
  53. 53.
    Rocha N, Kuijl C, van der Kant R, Janssen L, Houben D, Janssen H, Zwart W, Neefjes J (2009) Cholesterol sensor ORP1L contacts the ER protein VAP to control Rab7–RILP–p150Glued and late endosome positioning. J Cell Biol 185:1209–1225PubMedCrossRefPubMedCentralGoogle Scholar
  54. 54.
    Johansson M, Rocha N, Zwart W, Jordens I, Janssen L, Kuijl C, Olkkonen VM, Neefjes J (2007) Activation of endosomal dynein motors by stepwise assembly of Rab7-RILP-p150Glued, ORP1L, and the receptor betalll spectrin. J Cell Biol 176:459–471PubMedCrossRefPubMedCentralGoogle Scholar
  55. 55.
    van der Kant R, Fish A, Janssen L, Janssen H, Krom S, Ho N, Brummelkamp T, Carette J, Rocha N, Neefjes J (2013) Late endosomal transport and tethering are coupled processes controlled by RILP and the cholesterol sensor ORP1L. J Cell Sci 126:3462–3474PubMedCrossRefGoogle Scholar
  56. 56.
    Zhao K, Ridgway ND (2017) Oxysterol-binding protein-related protein 1L regulates cholesterol egress from the endo-lysosomal system. Cell Rep. 19:1807–1818PubMedCrossRefGoogle Scholar
  57. 57.
    Walther TC, Chung J, Jr RV (2016) Lipid droplet biogenesis. Annu Rev Cell Dev Biol 33:1–20Google Scholar
  58. 58.
    Hynynen R, Suchanek M, Spandl J, Bäck N, Thiele C, Olkkonen VM (2009) OSBP-related protein 2 is a sterol receptor on lipid droplets that regulates the metabolism of neutral lipids. J Lipid Res 50:1305–1315PubMedCrossRefPubMedCentralGoogle Scholar
  59. 59.
    Weber-Boyvat M, Kentala H, Peränen J, Olkkonen VM (2015) Ligand-dependent localization and function of ORP-VAP complexes at membrane contact sites. Cell Mol Life Sci 72:1967–1987PubMedCrossRefGoogle Scholar
  60. 60.
    Escajadillo T, Wang H, Li L, Li D, Sewer MB (2016) Oxysterol-related-binding-protein related Protein-2 (ORP2) regulates cortisol biosynthesis and cholesterol homeostasis. Mol Cell Endocrinol 427:73–85PubMedCrossRefPubMedCentralGoogle Scholar
  61. 61.
    Käkelä R, Tanhuanpää K, Laitinen S, Somerharju P, Olkkonen VM (2005) Overexpression of OSBP-related protein 2 (ORP2) in CHO cells induces alterations of phospholipid species composition. Biochem Cell Biol 83:677–683PubMedCrossRefGoogle Scholar
  62. 62.
    Laitinen S, Lehto M, Lehtonen S, Hyvärinen K, Heino S, Lehtonen E, Ehnholm C, Ikonen E, Olkkonen VM (2002) ORP2, a homolog of oxysterol binding protein, regulates cellular cholesterol metabolism. J Lipid Res 43:245–255PubMedGoogle Scholar
  63. 63.
    Hynynen R, Laitinen S, Käkelä R, Tanhuanpää K, Lusa S, Ehnholm C, Somerharju P, Ikonen E, Olkkonen VM (2005) Overexpression of OSBP-related protein 2 (ORP2) induces changes in cellular cholesterol metabolism and enhances endocytosis. Biochem J 390:273–283PubMedCrossRefPubMedCentralGoogle Scholar
  64. 64.
    Loilome W, Wechagama P, Namwat N, Jusakul A, Sripa B, Miwa M, Kuver R, Yongvanit P (2012) Expression of oxysterol binding protein isoforms in opisthorchiasis-associated cholangiocarcinoma: a potential molecular marker for tumor metastasis. Parasitol Int 61:136–139PubMedCrossRefGoogle Scholar
  65. 65.
    Silva N, Fournier M, Pimenta G, Pulcheri W, Spector N, da Carvalho M (2003) HLM/OSBP2 is expressed in chronic myeloid leukemia. Int J Mol Med 12:663–666Google Scholar
  66. 66.
    Fournier MV, da Costa GF, Paschoal ME, Ronco LV, Carvalho MG, Pardee AB, Giumaraes FC (1999) Identification of a gene encoding a human oxysterol-binding protein-homologue: a potential general molecular marker for blood dissemination of solid tumors. Cancer Res 59:3748–3753PubMedGoogle Scholar
  67. 67.
    Koga Y, Ishikawa S, Nakamura T, Masuda T, Nagai Y, Takamori H, Hirota M, Kanemitsu K, Baba Y, Baba H (2008) Oxysterol binding protein-related protein-5 is related to invasion and poor prognosis in pancreatic cancer. Cancer Sci 99:2387–2394PubMedCrossRefGoogle Scholar
  68. 68.
    Dmitriev AA, Rosenberg EE, Krasnov GS, Gerashchenko GV, Gordiyuk VV, Pavlova TV, Kudryavtseva AV, Beniaminov AD, Belova AA, Bondarenko YN, Danilets RO, Glukhov AI, Kondratov AG, Alexeyenko A, Alekseev BY, Klein G, Senchenko VN, Kashuba VI (2015) Identification of novel epigenetic markers of prostate cancer by NotI-microarray analysis. Dis Markers 2015:241301PubMedCrossRefPubMedCentralGoogle Scholar
  69. 69.
    Vozianov SO, Kashuba VI, Grygorenko VM, Gordiyuk VV, Danylets RO, Bondarenko YM, Vikarchuk MV (2016) Identification of a new diagnostic marker of prostatic cancer, using NOTI-microchips. Klin Khir 8:54–57Google Scholar
  70. 70.
    Lefebvre C, Bachelot T, Filleron T, Pedrero M, Campone M, Soria J-C, Massard C, Lévy C, Arnedos M, Lacroix-Triki M, Garrabey J, Boursin Y, Deloger M, Fu Y, Commo F, Scott V, Lacroix L, Dieci M, Kamal M, Diéras V, Gonçalves A, Ferrerro J-M, Romieu G, Vanlemmens L, Reynier M-A, Théry J-C, Du F, Guiu S, Dalenc F, Clapisson G, Bonnefoi H, Jimenez M, Tourneau C, André F (2016) Mutational profile of metastatic breast cancers: a retrospective analysis. PLoS Med 13:e1002201PubMedCrossRefPubMedCentralGoogle Scholar
  71. 71.
    Thoenes M, Zimmermann U, Ebermann I, Ptok M, Lewis MA, Thiele H, Morlot S, Hess MM, Gal A, Eisenberger T, Bergmann C, Nürnberg G, Nürnberg P, Steel KP, Knipper M, Bolz H (2015) OSBPL2 encodes a protein of inner and outer hair cell stereocilia and is mutated in autosomal dominant hearing loss (DFNA67). Orphanet J Rare Dis 10:15PubMedCrossRefPubMedCentralGoogle Scholar
  72. 72.
    Xing G, Yao J, Wu B, Liu T, Wei Q, Liu C, Lu Y, Chen Z, Zheng H, Yang X, Cao X (2014) Identification of OSBPL2 as a novel candidate gene for progressive nonsyndromic hearing loss by whole-exome sequencing. Genet Med 17:210–218PubMedCrossRefGoogle Scholar
  73. 73.
    Kentala H, Koponen A, Kivelä AM, Andrews R, Li C, Zhou Y, Olkkonen VM (2017) Analysis of ORP2 knockout hepatocytes uncovers a novel function in actin cytoskeletal regulation. FASEB J. CrossRefGoogle Scholar
  74. 74.
    Li D, Dammer EB, Lucki NC, Sewer MB (2013) cAMP-stimulated phosphorylation of diaphanous 1 regulates protein stability and interaction with binding partners in adrenocortical cells. Mol Biol Cell 24:848–857PubMedCrossRefPubMedCentralGoogle Scholar
  75. 75.
    Rudnicki A, Isakov O, Ushakov K, Shivatzki S, Weiss I, Friedman LM, Shomron N, Avraham KB (2014) Next-generation sequencing of small RNAs from inner ear sensory epithelium identifies microRNAs and defines regulatory pathways. BMC Genom 15:1–12CrossRefGoogle Scholar
  76. 76.
    Lynch ED, Lee MK, Morrow JE, Welcsh PL, León PE, King MC (1997) Nonsyndromic deafness DFNA1 associated with mutation of a human homolog of the Drosophila gene diaphanous. Science 278:1315–1318PubMedCrossRefGoogle Scholar
  77. 77.
    Kiernan MC, Vucic S, Cheah BC, Turner MR, Eisen A, Hardiman O, Burrell JR, Zoing MC (2011) Amyotrophic lateral sclerosis. Lancet 377:942–955PubMedCrossRefGoogle Scholar
  78. 78.
    Nishimura AL, Mitne-Neto M, Silva HCA, Richieri-Costa A, Middleton S, Cascio D, Kok F, Oliveira JRM, Gillingwater T, Webb J, Skehel P, Zatz M (2004) A mutation in the vesicle-trafficking protein VAPB causes late-onset spinal muscular atrophy and amyotrophic lateral sclerosis. Am J Hum Genet 75:822–831PubMedCrossRefPubMedCentralGoogle Scholar
  79. 79.
    Nishimura AL, Al-Chalabi A, Zatz M (2005) A common founder for amyotrophic lateral sclerosis type 8 (ALS8) in the Brazilian population. Hum Genet 118:499–500PubMedCrossRefGoogle Scholar
  80. 80.
    Darbyson A, Ngsee JK (2016) Oxysterol-binding protein ORP3 rescues the amyotrophic lateral sclerosis-linked mutant VAPB phenotype. Exp Cell Res 341:18–31PubMedCrossRefGoogle Scholar
  81. 81.
    Moustaqim-Barrette A, Lin YQ, Pradhan S, Neely GG, Bellen HJ, Tsuda H (2014) The amyotrophic lateral sclerosis 8 protein, VAP, is required for ER protein quality control. Hum Mol Genet 23:1975–1989PubMedCrossRefGoogle Scholar
  82. 82.
    Huang L-H, Elvington A, Randolph GJ (2015) The role of the lymphatic system in cholesterol transport. Front Pharmacol 6:182PubMedPubMedCentralGoogle Scholar
  83. 83.
    Stein S, Lemos V, Xu P, Demagny H, Wang X, Ryu D, Jimenez V, Bosch F, Lüscher TF, Oosterveer MH, Schoonjans K (2017) Impaired SUMOylation of nuclear receptor LRH-1 promotes nonalcoholic fatty liver disease. J Clin Investig 127:583–592PubMedCrossRefGoogle Scholar
  84. 84.
    Raitoharju E, Seppälä I, Lyytikäinen L-P, Viikari J, Ala-Korpela M, Soininen P, Kangas AJ, Waldenberger M, Klopp N, Illig T, Leiviskä J, Loo B-M, Oksala N, Kähönen M, Hutri-Kähönen N, Laaksonen R, Raitakari O, Lehtimäki T (2016) Blood hsa-miR-122-5p and hsa-miR-885-5p levels associate with fatty liver and related lipoprotein metabolism—the Young Finns Study. Sci Rep 6:38262PubMedCrossRefPubMedCentralGoogle Scholar
  85. 85.
    Perttilä J, Merikanto K, Naukkarinen J, Surakka I, Martin NW, Tanhuanpää K, Grimard V, Taskinen M-R, Thiele C, Salomaa V, Jula A, Perola M, Virtanen I, Peltonen L, Olkkonen VM (2009) OSBPL10, a novel candidate gene for high triglyceride trait in dyslipidemic Finnish subjects, regulates cellular lipid metabolism. J Mol Med 87:825–835PubMedCrossRefPubMedCentralGoogle Scholar
  86. 86.
    Koriyama H, Nakagami H, Katsuya T, Sugimoto K, Yamashita H, Takami Y, Maeda S, Kubo M, Takahashi A, Nakamura Y, Ogihara T, Rakugi H, Kaneda Y, Morishita R (2010) Identification of evidence suggestive of an association with peripheral arterial disease at the OSBPL10 locus by genome-wide investigation in the Japanese population. J Atheroscler Thromb 17:1054–1062PubMedCrossRefGoogle Scholar
  87. 87.
    Nissilä E, Ohsaki Y, Weber-Boyvat M, Perttilä J, Ikonen E, Olkkonen VM (2012) ORP10, a cholesterol binding protein associated with microtubules, regulates apolipoprotein B-100 secretion. BBA Mol Cell Biol Lipids 1821:1472–1484CrossRefGoogle Scholar
  88. 88.
    Motazacker MM, Pirhonen J, van Capelleveen JC, Weber-Boyvat M, Kuivenhoven J, Shah S, Hovingh KG, Metso J, Li S, Ikonen E, Jauhiainen M, Dallinga-Thie GM, Olkkonen VM (2016) A loss-of-function variant in OSBPL1A predisposes to low plasma HDL cholesterol levels and impaired cholesterol efflux capacity. Atherosclerosis 249:140–147PubMedCrossRefGoogle Scholar
  89. 89.
    Vihervaara T, Uronen R-L, Wohlfahrt G, Björkhem I, Ikonen E, Olkkonen VM (2011) Sterol binding by OSBP-related protein 1L regulates late endosome motility and function. Cell Mol Life Sci 68:537–551PubMedCrossRefGoogle Scholar
  90. 90.
    Zhong W, Pan G, Wang L, Li S, Ou J, Xu M, Li J, Zhu B, Cao X, Ma H, Li C, Xu J, Olkkonen VM, Staels B, Yan D (2016) ORP4L facilitates macrophage survival via G-protein-coupled signaling. Circ Res 119:1296–1312PubMedCrossRefGoogle Scholar
  91. 91.
    Yan D, Mäyränpää MI, Wong J, Perttilä J, Lehto M, Jauhiainen M, Kovanen PT, Ehnholm C, Brown AJ, Olkkonen VM (2008) OSBP-related protein 8 (ORP8) suppresses ABCA1 expression and cholesterol efflux from macrophages. J Biol Chem 283:332–340PubMedCrossRefGoogle Scholar
  92. 92.
    van Kampen E, Beaslas O, Hildebrand RB, Lammers B, Berkel TJC, Olkkonen VM, Eck M (2014) Orp8 deficiency in bone marrow-derived cells reduces atherosclerotic lesion progression in LDL receptor knockout mice. PLoS One 9:e109024PubMedCrossRefPubMedCentralGoogle Scholar
  93. 93.
    Zhou T, Li S, Zhong W, Vihervaara T, Béaslas O, Perttilä J, Luo W, Jiang Y, Lehto M, Olkkonen VM, Yan D (2011) OSBP-related Protein 8 (ORP8) regulates plasma and liver tissue lipid levels and interacts with the nucleoporin Nup62. PLoS One 6:e21078PubMedCrossRefPubMedCentralGoogle Scholar
  94. 94.
    Jordan SD, Krüger M, Willmes DM, Redemann N, Wunderlich TF, Brönneke HS, Merkwirth C, Kashkar H, Olkkonen VM, Böttger T, Braun T, Seibler J, Brüning JC (2011) Obesity-induced overexpression of miRNA-143 inhibits insulin-stimulated AKT activation and impairs glucose metabolism. Nat Cell Biol 13:434–446PubMedCrossRefGoogle Scholar
  95. 95.
    Blumensatt M, Greulich S, de Wiza D, Mueller H, Maxhera B, Rabelink MJ, Hoeben RC, Akhyari P, Al-Hasani H, Ruige JB, Ouwens MD (2013) Activin A impairs insulin action in cardiomyocytes via up-regulation of miR-143. Cardiovasc Res 100:201–210PubMedCrossRefGoogle Scholar
  96. 96.
    Blumensatt M, Wronkowitz N, Wiza C, Cramer A, Mueller H, Rabelink MJ, Hoeben RC, Eckel J, Sell H, Ouwens MD (2014) Adipocyte-derived factors impair insulin signaling in differentiated human vascular smooth muscle cells via the upregulation of miR-143. BBA Mol Basis Dis 1842:275–283CrossRefGoogle Scholar
  97. 97.
    Bouchard L, Faucher G, Tchernof A, Deshaies Y, Marceau S, Lescelleur O, Biron S, Bouchard C, Pérusse L, Vohl MC (2009) Association of OSBPL11 gene polymorphisms with cardiovascular disease risk factors in obesity. Obesity 17:1466–1472PubMedCrossRefGoogle Scholar
  98. 98.
    Kara B, Köroğlu Ç, Peltonen K, Steinberg RC, Genç H, Hölttä-Vuori M, Güven A, Kanerva K, Kotil T, Solakoğlu S, Zhou Y, Olkkonen VM, Ikonen E, Laiho M, Tolun A (2017) Severe neurodegenerative disease in brothers with homozygous mutation in POLR1A. Eur J Hum Genet 25:315–323PubMedCrossRefPubMedCentralGoogle Scholar
  99. 99.
    Zhou Y, Robciuc MR, Wabitsch M, Juuti A, Leivonen M, Ehnholm C, Yki-Järvinen H, Olkkonen VM (2012) OSBP-related proteins (ORPs) in human adipose depots and cultured adipocytes: evidence for impacts on the adipocyte phenotype. PLoS One 7:e45352PubMedCrossRefPubMedCentralGoogle Scholar
  100. 100.
    Egami H, Takiyama Y, Cano M, Houser WH, Pour PM (1989) Establishment of hamster pancreatic ductal carcinoma cell line (PC-1) producing blood group-related antigens. Carcinogenesis 10:861–869PubMedCrossRefGoogle Scholar
  101. 101.
    Pour PM, Egami H, Takiyama Y (1991) Patterns of growth and metastases of induced pancreatic cancer in relation to the prognosis and its clinical implications. Gastroenterology 100:529–536PubMedCrossRefGoogle Scholar
  102. 102.
    Ishikawa S, Nagai Y, Masuda T, Koga Y, Nakamura T, Imamura Y, Takamori H, Hirota M, Funakosi A, Fukushima M, Baba H (2010) The role of oxysterol binding protein-related protein 5 in pancreatic cancer. Cancer Sci 101:898–905PubMedCrossRefGoogle Scholar
  103. 103.
    Espenshade PJ (2006) SREBPs: sterol-regulated transcription factors. J Cell Sci 119:973–976PubMedCrossRefGoogle Scholar
  104. 104.
    Eckschlager T, Plch J, Stiborova M, Hrabeta J (2017) Histone deacetylase inhibitors as anticancer drugs. Int J Mol Sci 18:1414CrossRefPubMedCentralGoogle Scholar
  105. 105.
    Wajant H (2002) The Fas signaling pathway: more than a paradigm. Science 296:1635–1636PubMedCrossRefGoogle Scholar
  106. 106.
    Higaki K, Yano H, Kojiro M (1996) Fas antigen expression and its relationship with apoptosis in human hepatocellular carcinoma and noncancerous tissues. Am J Pathol 149:429–437PubMedPubMedCentralGoogle Scholar
  107. 107.
    Zhong W, Qin S, Zhu B, Pu M, Liu F, Wang L, Ye G, Yi Q, Yan D (2015) Oxysterol-binding protein-related protein 8 (ORP8) increases sensitivity of hepatocellular carcinoma cells to Fas-mediated apoptosis. J Biol Chem 290:8876–8887PubMedCrossRefPubMedCentralGoogle Scholar
  108. 108.
    Zhong W, Zhou Y, Li J, Mysore R, Luo W, Li S, Chang M-S, Olkkonen VM, Yan D (2014) OSBP-related protein 8 (ORP8) interacts with Homo sapiens sperm associated antigen 5 (SPAG5) and mediates oxysterol interference of HepG2 cell cycle. Exp Cell Res 322:227–235PubMedCrossRefGoogle Scholar
  109. 109.
    Silva N, Pimenta G, Pulcheri W, Fournier M, Spector N, da Carvalho CM (2001) Detection of messenger RNA in leukocytes or plasma of patients with chronic myeloid leukemia. Oncol Rep 8:693–696PubMedGoogle Scholar
  110. 110.
    Vlems FA, Diepstra JHS, Cornelissen I, Ligtenberg MJL, Wobbes T, Punt CJA, van Krieken J, Ruers TJM, van Muijen GNP (2003) Investigations for a multi-marker RT-PCR to improve sensitivity of disseminated tumor cell detection. Anticancer Res 23:179–186PubMedGoogle Scholar
  111. 111.
    Wang C, JeIley L, Ridgway ND (2002) Oxysterol-binding-protein (OSBP)-related protein 4 binds 25-hydroxycholesterol and interacts with vimentin intermediate filaments. Biochem J. 361:461–472PubMedCrossRefPubMedCentralGoogle Scholar
  112. 112.
    Wyles JP, Perry RJ, Ridgway ND (2007) Characterization of the sterol-binding domain of oxysterol-binding protein (OSBP)-related protein 4 reveals a novel role in vimentin organization. Exp Cell Res 313:1426–1437PubMedCrossRefGoogle Scholar
  113. 113.
    Charman M, Colbourne TR, Pietrangelo A, Kreplak L, Ridgway ND (2014) Oxysterol-binding protein (OSBP)-related protein 4 (ORP4) is essential for cell proliferation and survival. J Biol Chem 289:15705–15717PubMedCrossRefPubMedCentralGoogle Scholar
  114. 114.
    Lowery J, Kuczmarski ER, Herrmann H, Goldman RD (2015) Intermediate filaments play a pivotal role in regulating cell architecture and function. J Biol Chem 290:17145–17153PubMedCrossRefPubMedCentralGoogle Scholar
  115. 115.
    Li J-W, Xiao Y-L, Lai C-F, Lou N, Ma H-L, Zhu B-Y, Zhong W-B, Yan D-G (2016) Oxysterol-binding protein-related protein 4L promotes cell proliferation by sustaining intracellular Ca2+ homeostasis in cervical carcinoma cell lines. Oncotarget 7:65849–65861PubMedPubMedCentralGoogle Scholar
  116. 116.
    Zhong W, Yi Q, Xu B, Li S, Wang T, Liu F, Zhu B, Hoffmann PR, Ji G, Lei P, Li G, Li J, Li J, Olkkonen VM, Yan D (2016) ORP4L is essential for T-cell acute lymphoblastic leukemia cell survival. Nat Commun 7:12702PubMedCrossRefPubMedCentralGoogle Scholar
  117. 117.
    Udagawa O, Ito C, Ogonuki N, Sato H, Lee S, Tripvanuntakul P, Ichi I, Uchida Y, Nishimura T, Murakami M, Ogura A, Inoue T, Toshimori K, Arai H (2014) Oligo-astheno-teratozoospermia in mice lacking ORP4, a sterol-binding protein in the OSBP-related protein family. Genes Cells 19:13–27PubMedCrossRefGoogle Scholar
  118. 118.
    Miller S, Krijnse-Locker J (2008) Modification of intracellular membrane structures for virus replication. Nat Rev Microbiol 6:363–374PubMedCrossRefGoogle Scholar
  119. 119.
    Amako Y, Sarkeshik A, Hotta H, Yates J, Siddiqui A (2009) Role of oxysterol binding protein in hepatitis C virus infection. J Virol 83:9237–9246PubMedCrossRefPubMedCentralGoogle Scholar
  120. 120.
    Wang H, Perry JW, Lauring AS, Neddermann P, Francesco R, Tai AW (2014) Oxysterol-binding protein is a phosphatidylinositol 4-kinase effector required for HCV replication membrane integrity and cholesterol trafficking. Gastroenterology 146:1373–1385PubMedCrossRefPubMedCentralGoogle Scholar
  121. 121.
    Arita M (2014) Phosphatidylinositol-4 kinase III beta and oxysterol-binding protein accumulate unesterified cholesterol on poliovirus-induced membrane structure. Microbiol Immunol 58:239–256PubMedCrossRefGoogle Scholar
  122. 122.
    Dorobantu CM, Albulescu L, Harak C, Feng Q, van Kampen M, Strating JRPM, Gorbalenya AE, Lohmann V, van der Schaar HM, van Kuppeveld FJM (2015) Modulation of the host lipid landscape to promote RNA virus replication: the picornavirus encephalomyocarditis virus converges on the pathway used by hepatitis C virus. PLoS Pathog 11:e1005185PubMedCrossRefPubMedCentralGoogle Scholar
  123. 123.
    Albulescu L, Bigay J, Biswas B, Weber-Boyvat M, Dorobantu CM, Delang L, van der Schaar HM, Jung Y-S, Neyts J, Olkkonen VM, van Kuppeveld F, Strating J (2017) Uncovering oxysterol-binding protein (OSBP) as a target of the anti-enteroviral compound TTP-8307. Antivir Res 140:37–44PubMedCrossRefGoogle Scholar
  124. 124.
    Strating J, van der Linden L, Albulescu L, Bigay J, Arita M, Delang L, Leyssen P, van der Schaar HM, Lanke K, Thibaut H, Ulferts R, Drin G, Schlinck N, Wubbolts RW, Sever N, Head SA, Liu JO, Beachy PA, De Matteis MA, Shair MD, Olkkonen VM, Neyts J, van Kuppeveld F (2015) Itraconazole inhibits enterovirus replication by targeting the oxysterol-binding protein. Cell Rep 10:600–615PubMedCrossRefPubMedCentralGoogle Scholar
  125. 125.
    Albulescu L, Strating J, Thibaut H, van der Linden L, Shair MD, Neyts J, van Kuppeveld F (2015) Broad-range inhibition of enterovirus replication by OSW-1, a natural compound targeting OSBP. Antivir Res 117:110–114PubMedCrossRefGoogle Scholar
  126. 126.
    Park I-W, Ndjomou J, Wen Y, Liu Z, Ridgway ND, Kao CC, He JJ (2013) Inhibition of HCV replication by oxysterol-binding protein-related protein 4 (ORP4) through interaction with HCV NS5B and alteration of lipid droplet formation. PLoS One 8:e75648PubMedCrossRefPubMedCentralGoogle Scholar
  127. 127.
    Amini-Bavil-Olyaee S, Choi Y, Lee J, Shi M, Huang IC, Farzan M, Jung JU (2013) The antiviral effector IFITM3 disrupts intracellular cholesterol homeostasis to block viral entry. Cell Host Microbe 13:452–464PubMedCrossRefPubMedCentralGoogle Scholar
  128. 128.
    Sierra B, Triska P, Soares P, Garcia G, Perez AB, Aguirre E, Oliveira M, Cavadas B, Regnault B, Alvarez M, Ruiz D, Samuels DC, Sakuntabhai A, Pereira L, Guzman MG (2017) OSBPL10, RXRA and lipid metabolism confer African-ancestry protection against dengue haemorrhagic fever in admixed Cubans. PLoS Pathog 13:e1006220PubMedCrossRefPubMedCentralGoogle Scholar
  129. 129.
    Courtney SC, Di H, Stockman BM, Liu H, Scherbik SV, Brinton MA (2012) Identification of novel host cell binding partners of Oas1b, the protein conferring resistance to flavivirus-induced disease in mice. J Virol 86:7953–7963PubMedCrossRefPubMedCentralGoogle Scholar
  130. 130.
    Cianciola NL, Chung S, Manor D, Carlin CR (2017) Adenovirus modulates toll-like receptor 4 signaling by reprogramming ORP1L-VAP protein contacts for cholesterol transport from endosomes to the endoplasmic reticulum. J Virol 91:e01904PubMedCrossRefPubMedCentralGoogle Scholar
  131. 131.
    Cianciola NL, Greene DJ, Morton RE, Carlin CR (2013) Adenovirus RIDα uncovers a novel pathway requiring ORP1L for lipid droplet formation independent of NPC1. Mol Biol Cell 24:3309–3325PubMedCrossRefPubMedCentralGoogle Scholar
  132. 132.
    Wang P-Y, Weng J, Lee S, Anderson RGW (2008) The N terminus controls sterol binding while the C terminus regulates the scaffolding function of OSBP. J Biol Chem 283:8034–8045PubMedCrossRefGoogle Scholar
  133. 133.
    Moreira EF, Jaworski C, Li A, Rodriguez IR (2001) Molecular and biochemical characterization of a novel oxysterol-binding protein (OSBP2) highly expressed in retina. J Biol Chem 276:18570–18578PubMedCrossRefGoogle Scholar
  134. 134.
    Storey MK, Byers DM, Cook HW, Ridgway ND (1998) Cholesterol regulates oxysterol binding protein (OSBP) phosphorylation and Golgi localization in Chinese hamster ovary cells: correlation with stimulation of sphingomyelin synthesis by 25-hydroxycholesterol. Biochem J 336:247–256PubMedCrossRefPubMedCentralGoogle Scholar
  135. 135.
    Lehto M, Tienari J, Lehtonen S, Lehtonen E, Olkkonen VM (2004) Subfamily III of mammalian oxysterol-binding protein (OSBP) homologues: the expression and intracellular localization of ORP3, ORP6, and ORP7. Cell Tissue Res 315:39–57PubMedCrossRefGoogle Scholar
  136. 136.
    Lehto M, Hynynen R, Karjalainen K, Kuismanen E, Hyvärinen K, Olkkonen VM (2005) Targeting of OSBP-related protein 3 (ORP3) to endoplasmic reticulum and plasma membrane is controlled by multiple determinants. Exp Cell Res 310:445–462PubMedCrossRefGoogle Scholar
  137. 137.
    Lehto M, Mäyränpää MI, Pellinen T, Ihalmo P, Lehtonen S, Kovanen PT, Groop P-H, Ivaska J, Olkkonen VM (2008) The R-Ras interaction partner ORP3 regulates cell adhesion. J Cell Sci 121:695–705PubMedCrossRefGoogle Scholar
  138. 138.
    Vihervaara T, Käkelä R, Liebisch G, Tarasov K, Schmitz G, Olkkonen VM (2013) Modification of the lipidome in RAW264.7 macrophage subjected to stable silencing of oxysterol-binding proteins. Biochimie 95:538–547PubMedCrossRefGoogle Scholar
  139. 139.
    Higashimoto K, Soejima H, Yatsuki H, Joh K, Uchiyama M, Obata Y, Ono R, Wang Y, Xin Z, Zhu X, Masuko S, Ishino F, Hatada I, Jinno Y, Iwasaka T, Katsuki T, Mukai T (2002) Characterization and imprinting status of OBPH1/Obph1 gene: implications for an extended imprinting domain in human and mouse. Genomics 80:575–584PubMedCrossRefGoogle Scholar
  140. 140.
    Chung J, Torta F, Masai K, Lucast L, Czapla H, Tanner LB, Narayanaswamy P, Wenk MR, Nakatsu F, Camilli P (2015) PI4P/phosphatidylserine countertransport at ORP5- and ORP8-mediated ER–plasma membrane contacts. Science 349:428–432PubMedCrossRefPubMedCentralGoogle Scholar
  141. 141.
    Maeda K, Anand K, Chiapparino A, Kumar A, Poletto M, Kaksonen M, Gavin A-CC (2013) Interactome map uncovers phosphatidylserine transport by oxysterol-binding proteins. Nature 501:257–261PubMedCrossRefGoogle Scholar
  142. 142.
    Wyles JP, Ridgway ND (2004) VAMP-associated protein-A regulates partitioning of oxysterol-binding protein-related protein-9 between the endoplasmic reticulum and Golgi apparatus. Exp Cell Res 297:533–547PubMedCrossRefGoogle Scholar
  143. 143.
    Ngo M, Ridgway ND (2009) Oxysterol binding protein–related protein 9 (ORP9) is a cholesterol transfer protein that regulates golgi structure and function. Mol Biol Cell 20:1388–1399PubMedCrossRefPubMedCentralGoogle Scholar
  144. 144.
    Liu X, Ridgway ND (2014) Characterization of the sterol and phosphatidylinositol 4-phosphate binding properties of Golgi-associated OSBP-related protein 9 (ORP9). PLoS One 9:e108368PubMedCrossRefPubMedCentralGoogle Scholar
  145. 145.
    Zhou Y, Li S, Mäyränpää MI, Zhong W, Bäck N, Yan D, Olkkonen VM (2010) OSBP-related protein 11 (ORP11) dimerizes with ORP9 and localizes at the Golgi-late endosome interface. Exp Cell Res 316:3304–3316PubMedCrossRefGoogle Scholar
  146. 146.
    Erdem-Eraslan L, van den Bent MJ, Hoogstrate Y, Naz-Khan H, Stubbs A, van der Spek P, Böttcher R, Gao Y, de Wit M, Taal W, Oosterkamp HM, Walenkamp A, Beerepoot LV, Hanse M, Buter J, Honkoop AH, van der Holt B, Vernhout RM, Smitt P, Kros JM, French PJ (2016) Identification of patients with recurrent glioblastoma who may benefit from combined bevacizumab and CCNU therapy: a report from the BELOB Trial. Cancer Res 76:525–534PubMedCrossRefGoogle Scholar
  147. 147.
    Li H, Wang X, Fang Y, Huo Z, Lu X, Zhan X, Deng X, Peng C, Shen B (2014) Integrated expression profiles analysis reveals novel predictive biomarker in pancreatic ductal adenocarcinoma. Oncotarget 5Google Scholar
  148. 148.
    Nagano K, Imai S, Zhao X, Yamashita T, Yoshioka Y, Abe Y, Mukai Y, Kamada H, Nakagawa S, Tsutsumi Y, Tsunoda S-I (2015) Identification and evaluation of metastasis-related proteins, oxysterol binding protein-like 5 and calumenin, in lung tumors. Int J Oncol 47:195–203PubMedCrossRefGoogle Scholar
  149. 149.
    Edenberg HJ, Koller DL, Xuei X, Wetherill L, McClintick JN, Almasy L, Bierut LJ, Bucholz KK, Goate A, Aliev F, Dick D, Hesselbrock V, Hinrichs A, Kramer J, Kuperman S, Nurnberger JI, Rice JP, Schuckit MA, Taylor R, Webb TB, Tischfield JA, Porjesz B, Foroud T (2010) Genome-wide association study of alcohol dependence implicates a region on chromosome 11. Alcohol Clin Exp Res 34:840–852PubMedCrossRefPubMedCentralGoogle Scholar
  150. 150.
    Ma J, Dempsey AA, Stamatiou D, Marshall KW, Liew C-C (2007) Identifying leukocyte gene expression patterns associated with plasma lipid levels in human subjects. Atherosclerosis 191:63–72PubMedCrossRefGoogle Scholar
  151. 151.
    Herold C, Hooli BV, Mullin K, Liu T, Roehr JT, Mattheisen M, Parrado AR, Bertram L, Lange C, Tanzi RE (2016) Family-based association analyses of imputed genotypes reveal genome-wide significant association of Alzheimer’s disease with OSBPL6, PTPRG, and PDCL3. Mol Psychiatry 21:1608–1612PubMedCrossRefPubMedCentralGoogle Scholar
  152. 152.
    Teslovich TM, Musunuru K, Smith AV, Edmondson AC, Stylianou IM, Koseki M, Pirruccello JP, Ripatti S, Chasman DI, Willer CJ, Johansen CT, Fouchier SW, Isaacs A, Peloso GM, Barbalic M, Ricketts SL, Bis JC, Aulchenko YS, Thorleifsson G, Feitosa MF, Chambers J, Orho-Melander M, Melander O, Johnson T, Li X, Guo X, Li M, Shin Cho Y, Jin Go M, Jin Kim Y, Lee JY, Park T, Kim K, Sim X, Twee-Hee Ong R, Croteau-Chonka DC, Lange LA, Smith JD, Song K, Hua Zhao J, Yuan X, Luan J, Lamina C, Ziegler A, Zhang W, Zee RY, Wright AF, Witteman JC, Wilson JF, Willemsen G, Wichmann HE, Whitfield JB, Waterworth DM, Wareham NJ, Waeber G, Vollenweider P, Voight BF, Vitart V, Uitterlinden AG, Uda M, Tuomilehto J, Thompson JR, Tanaka T, Surakka I, Stringham HM, Spector TD, Soranzo N, Smit JH, Sinisalo J, Silander K, Sijbrands EJ, Scuteri A, Scott J, Schlessinger D, Sanna S, Salomaa V, Saharinen J, Sabatti C, Ruokonen A, Rudan I, Rose LM, Roberts R, Rieder M, Psaty BM, Pramstaller PP, Pichler I, Perola M, Penninx BW, Pedersen NL, Pattaro C, Parker AN, Pare G, Oostra BA, O’Donnell CJ, Nieminen MS, Nickerson DA, Montgomery GW, Meitinger T, McPherson R, McCarthy MI et al (2010) Biological, clinical and population relevance of 95 loci for blood lipids. Nature 466:707–713PubMedCrossRefPubMedCentralGoogle Scholar
  153. 153.
    Willer G, Schmidt CJ, Sengupta EM, Peloso S, Gustafsson GM, Kanoni S, Ganna S, Chen A, Buchkovich J, Mora ML, Beckmann S, Bragg-Gresham JS, Chang JL, Demirkan H-Y, Hertog A, Do HM, Donnelly R, Ehret LA, Esko GB, Feitosa T, Ferreira MF, Fischer T, Fontanillas K, Fraser P, Freitag RM, Gurdasani DF, Heikkilä D, Hyppönen K, Isaacs E, Jackson A, Johansson AU, Johnson A, Kaakinen T, Kettunen M, Kleber J, Li ME, Luan X, Lyytikäinen JA, Magnusson L-P, Mangino PKE, Mihailov M, Montasser E, Müller-Nurasyid ME, Nolte M, O’Connell IM, Palmer JR, Perola CD, Petersen M, Sanna A-K, Saxena S, Service R, Shah SK, Shungin S, Sidore D, Song C, Strawbridge C, Surakka RJ, Tanaka I, Teslovich T, Thorleifsson TM, den Herik G, Voight EG, Volcik BF, Waite KA, Wong LL, Wu A, Zhang Y, Absher W, Asiki D, Barroso G, Been I, Bolton LF, Bonnycastle JL, Brambilla LL, Burnett P, Cesana MS, Dimitriou G, Doney M, Döring ASF, Elliott A, Epstein P, Eyjolfsson SE, Gigante G, Goodarzi B, Grallert MO, Gravito H, Groves ML, Hallmans CJ, Hartikainen G, Hayward A-L, Hernandez C, Hicks D, Holm AA, Hung H, Illig Y-J, Jones T, Kaleebu MR, Kastelein P, Khaw JJP et al (2013) Discovery and refinement of loci associated with lipid levels. Nat Genet 45:1274–1283Google Scholar
  154. 154.
    Guo X, Zhang L, Zhang Y, Zhang D, Qin L, Dong S, Li G (2016) Oxysterol binding protein-related protein 8 inhibits gastric cancer growth through induction of ER stress, inhibition of Wnt signaling and activation of apoptosis. Oncol Res 25:799–808PubMedCrossRefGoogle Scholar
  155. 155.
    Ma L, Yang J, Runesha BH, Tanaka T, Ferrucci L, Bandinelli S, Da Y (2010) Genome-wide association analysis of total cholesterol and high-density lipoprotein cholesterol levels using the Framingham Heart Study data. BMC Med Genet 11:1–11Google Scholar
  156. 156.
    Sohn M, Ivanova P, Brown AH, Toth DJ, Varnai P, Kim Y, Balla T (2016) Lenz-Majewski mutations in PTDSS1 affect phosphatidylinositol 4-phosphate metabolism at ER-PM and ER-Golgi junctions. Proc Natl Acad Sci USA 113:4314–4319PubMedCrossRefGoogle Scholar
  157. 157.
    Aziz N, Mokhtar NM, Harun R, Mollah M, Rose I, Sagap I, Tamil A, Ngah W, Jamal R (2016) A 19-Gene expression signature as a predictor of survival in colorectal cancer. BMC Med Genet 9:58Google Scholar
  158. 158.
    Li L, Qu G, Wang M, Huang Q, Liu Y (2014) Association of oxysterol binding protein-related protein 9 polymorphism with cerebral infarction in Hunan Han population. Ir J Med Sci 183:439–448PubMedCrossRefGoogle Scholar
  159. 159.
    Koriyama H, Nakagami H, Katsuya T, Akasaka H, Saitoh S, Shimamoto K, Ogihara T, Kaneda Y, Morishita R, Rakugi H (2010) Variation in OSBPL10 is associated with dyslipidemia. Hypertens Res 33:511–514PubMedCrossRefGoogle Scholar
  160. 160.
    Stewart WCL, Huang Y, Greenberg DA, Vieland VJ (2014) Next-generation linkage and association methods applied to hypertension: a multifaceted approach to the analysis of sequence data. BMC Proc 8:1–4CrossRefGoogle Scholar

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© Springer International Publishing AG, part of Springer Nature 2018

Authors and Affiliations

  1. 1.Atlantic Research Center, C306 CRC Bldg, Department of Pediatrics, and Biochemistry and Molecular BiologyDalhousie UniversityHalifaxCanada

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