HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Permissions Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Mohammadi, A. Articles by Ridgway, N. D. Search for Related Content PubMed PubMed Citation Articles by Mohammadi, A. Articles by Ridgway, N. D. Social Bookmarking                      What's this?

Journal of Lipid Research, Vol. 42, 1062-1071, July 2001
Copyright © 2001 by Lipid Research, Inc.

Original Article

Golgi localization and phosphorylation of oxysterol binding protein in Niemann-Pick C and U18666A-treated cells

Correspondence to: Neale D. Ridgway, To whom correspondence should be addressed., nridgway{at}is.dal.ca (E-mail)

Oxysterol binding protein (OSBP) translocation between Golgi and vesicular/cytoplasmic compartments is affected by conditions that alter cholesterol and sphingomyelin homeostasis, indicating a role in lipid and sterol regulation in this organelle. In this study, we show that OSBP dissociation from the Golgi apparatus was inhibited when LDL cholesterol efflux from lysosomes was blocked in Niemann-Pick C (NPC) or U18666A {3-ß-[2-(diethylamino)ethoxy]androst-5-en-17-one}-treated fibroblasts. Dissociation of OSBP from the Golgi apparatus in response to LDL was independent of de novo cholesterol biosynthesis. OSBP did not localize with filipin-stained lysosomal cholesterol, and the NPC defect did not alter OSBP expression or phosphorylation. However, OSBP in the Golgi apparatus was progressively dephosphorylated (as assessed by a molecular mass shift on SDS-PAGE) in U18666A-treated fibroblasts or Chinese hamster ovary cells as a result of combined inhibition of LDL cholesterol transport and de novo cholesterol synthesis. In vivo phosphopeptide mapping and mutagenesis of OSBP was used to identify the cholesterol-sensitive phosphorylation sites at serines 381, 384, and 387 that were responsible for the altered mobility on SDS-PAGE.

NPC-1 protein-mediated release of LDL-derived cholesterol and de novo biosynthesis regulates OSBP localization and phosphorylation. This indicates that OSBP responds to or senses altered cellular sterol content and transport. — Mohammadi, A., R. J. Perry, M. K. Storey, H. W. Cook, D. M. Byers, and N. D. Ridgway. Golgi localization and phosphorylation of oxysterol binding protein in Niemann-Pick C and U18666A-treated cells. J. Lipid Res. 2001. 42: 1062;–1071.

Supplementary key words: Niemann-Pick type C, cholesterol, Golgi apparatus

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

This article has been cited by other articles:

				M. Ngo and N. D. Ridgway Oxysterol Binding Protein-related Protein 9 (ORP9) Is a Cholesterol Transfer Protein That Regulates Golgi Structure and Function Mol. Biol. Cell, March 1, 2009; 20(5): 1388 - 1399. [Abstract] [Full Text] [PDF]

				K. Bowden and N. D. Ridgway OSBP Negatively Regulates ABCA1 Protein Stability J. Biol. Chem., June 27, 2008; 283(26): 18210 - 18217. [Abstract] [Full Text] [PDF]

				P.-Y. Wang, J. Weng, S. Lee, and R. G. W. Anderson The N Terminus Controls Sterol Binding while the C Terminus Regulates the Scaffolding Function of OSBP J. Biol. Chem., March 21, 2008; 283(12): 8034 - 8045. [Abstract] [Full Text] [PDF]

				K. Kumagai, M. Kawano, F. Shinkai-Ouchi, M. Nishijima, and K. Hanada Interorganelle Trafficking of Ceramide Is Regulated by Phosphorylation-dependent Cooperativity between the PH and START Domains of CERT J. Biol. Chem., June 15, 2007; 282(24): 17758 - 17766. [Abstract] [Full Text] [PDF]

				R. J. Perry and N. D. Ridgway Oxysterol-binding Protein and Vesicle-associated Membrane Protein-associated Protein Are Required for Sterol-dependent Activation of the Ceramide Transport Protein Mol. Biol. Cell, June 1, 2006; 17(6): 2604 - 2616. [Abstract] [Full Text] [PDF]

				P.-y. Wang, J. Weng, and R. G. W. Anderson OSBP Is a Cholesterol-Regulated Scaffolding Protein in Control of ERK1/2 Activation Science, March 4, 2005; 307(5714): 1472 - 1476. [Abstract] [Full Text] [PDF]

				R. E. Soccio and J. L. Breslow Intracellular Cholesterol Transport Arterioscler. Thromb. Vasc. Biol., July 1, 2004; 24(7): 1150 - 1160. [Abstract] [Full Text] [PDF]

				R. J. Perry and N. D. Ridgway The role of de novo ceramide synthesis in the mechanism of action of the tricyclic xanthate D609 J. Lipid Res., January 1, 2004; 45(1): 164 - 173. [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]

				J. P. Wyles, C. R. McMaster, and N. D. Ridgway 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., August 9, 2002; 277(33): 29908 - 29918. [Abstract] [Full Text] [PDF]