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

J. Biol. Chem., Vol. 281, Issue 32, 23191-23206, August 11, 2006

This Article Full Text Full Text (PDF) All Versions of this Article: 281/32/23191    most recent M603215200v1 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 Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Sugii, S. Articles by Chang, T.-Y. Search for Related Content PubMed PubMed Citation Articles by Sugii, S. Articles by Chang, T.-Y. Social Bookmarking                      What's this?

Roles of Endogenously Synthesized Sterols in the Endocytic Pathway^*

Shigeki Sugii¹², Song Lin¹, Nobutaka Ohgami¹³, Masato Ohashi, Catherine C. Y. Chang, and Ta-Yuan Chang⁴

From the Department of Biochemistry, Dartmouth Medical School, Hanover, New Hampshire 03755 and Okazaki Institute for Integrative Bioscience, National Institutes of Natural Sciences, Okazaki 444-8787, Japan

The effect(s) of endogenously synthesized cholesterol (endo-CHOL) on the endosomal system in mammalian cells has not been examined. Here we treated Chinese hamster ovary cell lines with lovastatin (a hydroxymethylglutaryl-CoA reductase inhibitor) and mevalonate (a precursor for isoprenoids) to block endo-CHOL synthesis and then examined its effects on the fate of cholesterol liberated from low density lipoprotein (LDL-CHOL). The results showed that blocking endo-CHOL synthesis for 2 h or longer does not impair the hydrolysis of cholesteryl esters but partially impairs the transport of LDL-CHOL to the plasma membrane. Blocking endo-CHOL synthesis for 2 h or longer also alters the localization patterns of the late endosomes/lysosomes and retards their motility, as monitored by time-lapse microscopy. LDL-CHOL overcomes the effect of blocking endo-CHOL synthesis on endosomal localization patterns and on endosomal motility. Overexpressing Rab9, a key late endosomal small GTPase, relieves the endosomal cholesterol accumulation in Niemann-Pick type C1 cells but does not revert the reduced endosomal motility caused by blocking endo-CHOL synthesis. Our results suggested that endo-CHOL contributes to the cholesterol content of late endosomes and controls its motility, in a manner independent of NPC1. These results also supported the concept that endosomal motility plays an important role in controlling cholesterol trafficking activities.

Received for publication, April 4, 2006 , and in revised form, May 30, 2006.

^* This work was supported in part by National Institutes of Health Grant HL36709 (to T.-Y. C.). The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked "advertisement" in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

¹ These authors contributed equally to this work.

² Present address: Gene Expression Laboratory, The Salk Institute for Biological Studies and Howard Hughes Medical Institute, La Jolla, CA 92037.

³ Supported by a postdoctoral fellowship from the National Niemann-Pick Foundation. Present address: Dept. of Environmental Health Sciences, Chubu University, Aichi 487-8501, Japan.

⁴ To whom correspondence should be addressed. Tel.: 603-650-1622; Fax: 603-650-1128; E-mail: Ta.Yuan.Chang{at}dartmouth.edu.

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

This article has been cited by other articles:

				J. Wright, M. M. Morales, J. Sousa-Menzes, D. Ornellas, J. Sipes, Y. Cui, I. Cui, P. Hulamm, V. Cebotaru, L. Cebotaru, et al. Transcriptional adaptation to Clcn5 knockout in proximal tubules of mouse kidney Physiol Genomics, May 9, 2008; 33(3): 341 - 354. [Abstract] [Full Text] [PDF]

				Y. Yamauchi, P. C. Reid, J. B. Sperry, K. Furukawa, M. Takeya, C. C. Y. Chang, and T.-Y. Chang Plasma Membrane Rafts Complete Cholesterol Synthesis by Participating in Retrograde Movement of Precursor Sterols J. Biol. Chem., November 30, 2007; 282(48): 34994 - 35004. [Abstract] [Full Text] [PDF]