Original Article

Family of human oxysterol binding protein (OSBP) homologues: a novel member implicated in brain sterol metabolism

Correspondence to: Elina Ikonen

Oxysterol binding protein (OSBP) is a cytosolic protein that undergoes ligand-induced binding to the Golgi apparatus and has been implicated in the regulation of cellular cholesterol metabolism. In the yeast Saccharomyces cerevisiae an OSBP homologue is involved in membrane trafficking through the Golgi complex. Prompted by the multitude of OSBP-related genes in the yeast genome, we carried out a search for human expressed sequence tags (ESTs) displaying homology to the sterol-binding domain of OSBP. This revealed a minimum of six novel OSBP-related proteins, designated ORP-1 to ORP-6. ORP cDNA probes were generated by reverse transcription-PCR from human liver mRNA, and used for Northern blot analysis of human tissue transcript panels. This verified that each of them represents a different gene product and showed that they display distinct tissue-specific expression patterns. The ORP-1 and -2 mRNA expression levels were similar to or higher than that of OSBP while the ORP-3 to -6 mRNAs were detected at lower levels in specific tissues.

The most abundantly expressed new gene, ORP-1, was transcribed at strikingly high levels in the cortical areas of human brain and displayed sterol-regulated expression in a cultured human neuroblastoma cell line. This indicates that ORP-1 may play an important role in maintaining the sterol balance in cells of the central nervous system. Together with OSBP, the identified gene products constitute a novel human protein family that may provide a link between organellar sterol status and membrane dynamics.—Laitinen, S., V. M. Olkkonen, C. Ehnholm, and E. Ikonen. Family of human oxysterol binding protein (OSBP) homologues: a novel member implicated in brain sterol metabolism. J. Lipid Res. 1999: 40: 2204;–2211.

Supplementary key words: cholesterol metabolism, membrane transport, hydroxycholesterol, brain cholesterol

CiteULike    Complore    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this?

This article has been cited by other articles:

				A. Malhotra, J. K. Wolford, and the American Diabetes Association GENNID Study Gro Analysis of Quantitative Lipid Traits in the Genetics of NIDDM (GENNID) Study Diabetes, October 1, 2005; 54(10): 3007 - 3014. [Abstract] [Full Text] [PDF]

				J. Silva, A. Beckedorf, and E. Bieberich Osteoblast-derived Oxysterol Is a Migration-inducing Factor for Human Breast Cancer Cells J. Biol. Chem., July 3, 2003; 278(28): 25376 - 25385. [Abstract] [Full Text] [PDF]

				M. de Chaldee, M.-C. Gaillard, N. Bizat, J.-M. Buhler, O. Manzoni, J. Bockaert, P. Hantraye, E. Brouillet, and J.-M. Elalouf Quantitative Assessment of Transcriptome Differences Between Brain Territories Genome Res., July 1, 2003; 13(7): 1646 - 1653. [Abstract] [Full Text] [PDF]

				M. Johansson, V. Bocher, M. Lehto, G. Chinetti, E. Kuismanen, C. Ehnholm, B. Staels, and V. M. Olkkonen 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, March 1, 2003; 14(3): 903 - 915. [Abstract] [Full Text] [PDF]

				I. Bjorkhem and U. Diczfalusy Oxysterols: Friends, Foes, or Just Fellow Passengers? Arterioscler. Thromb. Vasc. Biol., May 1, 2002; 22(5): 734 - 742. [Abstract] [Full Text] [PDF]

				S. Laitinen, M. Lehto, S. Lehtonen, K. Hyvarinen, S. Heino, E. Lehtonen, C. Ehnholm, E. Ikonen, and V. M. Olkkonen ORP2, a homolog of oxysterol binding protein, regulates cellular cholesterol metabolism J. Lipid Res., February 1, 2002; 43(2): 245 - 255. [Abstract] [Full Text] [PDF]

				C. C. Gregorio-King, G. R. Collier, J. S. McMillan, C. M. Waugh, J. L. McLeod, F. M. Collier, and M. A. Kirkland ORP-3, a human oxysterol-binding protein gene differentially expressed in hematopoietic cells Blood, October 1, 2001; 98(7): 2279 - 2281. [Abstract] [Full Text] [PDF]

				M. Lehto, S. Laitinen, G. Chinetti, M. Johansson, C. Ehnholm, B. Staels, E. Ikonen, and V. M. Olkkonen The OSBP-related protein family in humans J. Lipid Res., August 1, 2001; 42(8): 1203 - 1213. [Abstract] [Full Text] [PDF]

				K. Simons and E. Ikonen How Cells Handle Cholesterol Science, December 1, 2000; 290(5497): 1721 - 1726. [Abstract] [Full Text]

				E. F. Moreira, C. Jaworski, A. Li, and I. R. Rodriguez Molecular and Biochemical Characterization of a Novel Oxysterol-binding Protein (OSBP2) Highly Expressed in Retina J. Biol. Chem., May 18, 2001; 276(21): 18570 - 18578. [Abstract] [Full Text] [PDF]