Research
The present main project of the group deals with the mechanisms that the cell uses to sense its lipid status and to relay this information to regulate (i) expression of the genes and activity of the enzymes of lipid metabolism as well as (ii) other processes affected by the lipid composition of membranes. Such processes are for example intracellular vesicle transport responsible for trafficking of molecules between subcellular organelles and signal transduction events. Oxysterols are oxidized derivatives of cholesterol that act as potent regulators of cellular lipid metabolism. They also have a multitude of other cellular effects, for instance on cell survival, signaling and differentiation processes, and they are found enriched in atherosclerotic lesions. We have identified a family of 12 human genes that encode oxysterol-binding proteins, ORPs. Our work focuses on the elucidation of the function of these proteins in the control of cellular lipid metabolism and in the development of atherosclerotic diseases, as well as the putative role of their genetic variation in dyslipidemias. We also investigate their wider functional connections, for instance with intracellular transport processes and the inflammatory functions of macrophages. To reach our goals we employ a spectrum of methods from molecular cell biology approaches and laboratory animal models to human genetics.
KTL Cell Imaging Unit
Research group:
Vesa Olkkonen, Ph.D., Docent
Olivier Beaslas, Ph.D.
Riikka Hynynen, M.Sc.
Julia Perttilä, Ph.D.
Seija Puomilahti, technician
Pirjo Ranta, technician
Terhi Vihervaara, M.Sc.
You Zhou, M.Sc.
Most important publications
- Olkkonen, V.M. and Ikonen, E. (2000)
Genetic defects of intracellular-membrane transport.
New Engl. J. Med.
343,
1095-1104.
PubMed
- Lehto, M., Laitinen, S., Chinetti, G., Johansson, M., Ehnholm, C., Staels, B., Ikonen, E. and Olkkonen, V.M. (2001)
The OSBP-related protein family in humans
. J. Lipid Res.
42, 1203-1213.
PubMed
- Johansson, M., Bocher, V., Lehto, M., Chinetti, G., Kuismanen, E., Ehnholm.
C., Staels, B. and Olkkonen, V.M. (2003) The two variants of OSBP-related protein-1 (ORP1) display different tissue expression patterns, have different intracellular localization, and are functionally distinct.
Mol. Biol. Cell
14, 903-915.
PubMed
- Hynynen, R., Laitinen, S., Käkelä, R., Tanhuanpää, K., Lusa, S., Ehnholm.
C., Somerharju, P., Ikonen E. and Olkkonen, V.M. (2005) Overexpression of OSBP-related protein 2 (ORP2) induces changes in cellular cholesterol metabolism and enhances endocytosis.
Biochem
390, 273-283.
PubMed
- Johansson, M., Lehto, M., Tanhuanpää, K., Cover, T.L., and Olkkonen, V.M. (2005)
The Oxysterol-binding Protein Homologue ORP1L Interacts with Rab7 and Alters Functional Properties of the Late Endocytic Compartments.
Mol Biol Cell.
16, 5480-5492.
PubMed
- Johansson, M., Rocha, N., Zwart, W., Jordens, I., Janssen, L., Kuijl, C., Olkkonen, V.M. and Neefjes, J. (2007) Activation of endosomal dynein motors by stepwise assembly of Rab7-RILP-p150Glued, ORP1L and the receptor bIII spectrin.
J. Cell Biol. 176, 459-71.
PubMed
- Lam PP, Hyvärinen K, Kauppi M, Cosen-Binker L, Laitinen S, Keränen S, Gaisano HY, Olkkonen VM. (2007) A cytosolic splice variant of Cab45 interacts with Munc18b and impacts on amylase secretion by pancreatic acini.
Mol Biol Cell 18:2473-80.
PubMed
- Siggins S, Bykov I, Hermansson M, Somerharju P, Lindros K, Miettinen TA, Jauhiainen M, Olkkonen VM, Ehnholm C. (2007) Altered hepatic lipid status and apolipoprotein A-I metabolism in mice lacking phospholipid transfer protein.
Atherosclerosis 190:114-23.
PubMed
- Suchanek, M., Hynynen, R., Wohlfahrt, G., Lehto, M., Johansson, M., Saarinen, H., Radzikowska, A., Thiele, C., and Olkkonen, V.M. (2007) The mammalian OSBP-related proteins (ORP) bind 25-hydroxycholesterol in an evolutionarily conserved pocket.
Biochem. J.
2007 Aug 1;
405(
3):
473-80.
PubMed
- Vikstedt R, Metso J, Hakala J, Olkkonen VM, Ehnholm C, Jauhiainen M. (2007) Cholesterol efflux from macrophage foam cells is enhanced by active phospholipid transfer protein through generation of two types of acceptor particles.
Biochemistry 46:11979-86.
PubMed
- Yan, D., Lehto, M., Rasilainen, L., Metso, J., Ehnholm, C., Ylä-Herttuala, S., Jauhiainen, M., and Olkkonen, V.M. (2007) Oxysterol binding protein induces upregulation of SREBP-1c and enhances hepatic lipogenesis.
Arterioscler Thromb Vasc Biol. 27, 1108-14.
PubMed
- Yan, D., Jauhiainen, M., Hildebrand, R.B., van Dijk, K.W., Van Berkel, T.J.C., Ehnholm, C., Van Eck, M., and Olkkonen V.M. (2007) Expression of Human OSBP-Related Protein 1L in Macrophages Enhances Atherosclerotic Lesion Development in LDL Receptor-Deficient Mice.
Arterioscler Thromb Vasc Biol.
2007 Jul;
27(
7):
1618-24.
PubMed
- 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., 2008 Jan 4;
283(
1):
332-40.
PubMed
- Lehto M, Mäyränpää MI, Pellinen T, Ihalmo P, Lehtonen S, Kovanen PT, Groop PH, Ivaska J, Olkkonen VM. (2008) The R-Ras interaction partner ORP3 regulates cell adhesion.
J Cell Sci., 2008 Mar 1;121(Pt 5):695-705.
PubMed
Ph.D. Dissertations
Minna T. Jänis -
The High- and Low-activity Forms of Human Plasma Phospholipid Transfer Protein (PLTP). Publication of the National Public Health Institute, University of Helsinki, 2006. (Supervised by Adjunct Professor Matti Jauhiainen, Adjunct Professor Vesa Olkkonen and Research Professor Christian Ehnholm)
Marie Johansson -
ORP1L, a New Rab7 Effector and Regulator of Late Endosome Functions. Publication of the National Public Health Institute, University of Helsinki, 2006. (Supervised by Docent Vesa Olkkonen)
Sarah Siggins -
Plasma Phospholipid Transfer Protein (PLTP): Quantitation, Biosynthesis, and Involvement in Hepatic Lipid Homeostasis. Publication of the National Public Health Institute, University of Helsinki, 2005. (Supervised by Docent Vesa Olkkonen, Docent Matti Jauhiainen and Professor Christian Ehnholm)
Maria Kauppi -
Functional Characterisation Of Rab22a And Munc18b, Two Proteins Regulating Vesicle Transport In Mammalian Cells. Publication of the National Public Health Institute, University of Helsinki, 2004. (Supervised by Docent Vesa Olkkonen)
Sanna Heino - Transport Of Newly Synthesized Sterols to Extracellular Acceptors. Publication of the National Public Health Institute, University of Jyväskylä, 2003. (Supervised by Docent Elina Ikonen and Docent Vesa Olkkonen)
Sonja Jaari - Proteins Involved In High Density Lipoprotein Metabolism - A Special Reference To Apolipoprotein A-I, Hepatic Lipase And Phospholipid Transfer Protein. Publication of the National Public Health Institute, University of Helsinki, 2002. (Supervised by Docent Matti Jauhiainen and Docent Vesa Olkkonen)
Saara Laitinen -
Family Of Human Oxysterol Binding Protein Homologues: ORP2 Is A New Regulator Of Cellular Lipid Metabolism. Publication of the National Public Health Institute, University of Helsinki, 2002. (Supervised by Docent Vesa Olkkonen and Docent Elina Ikonen)
Jarkko Huuskonen - The Phospholipid Transfer Activity And Structural Features Of Human Plasma PLTP. Publication of the National Public Health Institute, University of Helsinki, 1999. (Supervised by Docent Vesa Olkkonen and Docent Matti Jauhiainen)
Kirsi Riento - Characterization Of Munc-18-2, A Mammalian Sec1 Protein. Publication of the National Public Health Institute, University of Helsinki, 1999. (Supervised by Docent Vesa Olkkonen) |
Additional information
Docent Vesa Olkkonen
e-mail: firstname.lastname@thl.fi
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