Journal of Biological Chemistry
Volume 276, Issue 45, 9 November 2001, Pages 41748-41754
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MEMBRANE TRANSPORT STRUCTURE FUNCTION AND BIOGENESIS
Inhibition of Protein Translocation across the Endoplasmic Reticulum Membrane by Sterols*

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Cholesterol and related sterols are known to modulate the physical properties of biological membranes and can affect the activities of membrane-bound protein complexes. Here, we report that an early step in protein translocation across the endoplasmic reticulum (ER) membrane is reversibly inhibited by cholesterol levels significantly lower than those found in the plasma membrane. By UV-induced chemical cross-linking we further show that high cholesterol levels prevent cross-linking between ribosome-nascent chain complexes and components of the Sec61 translocon, but have no effect on cross-linking to the signal recognition particle. The inhibiting effect on translocation is different between different sterols. Our data suggest that the protein translocation machinery may be sensitive to changes in cholesterol levels in the ER membrane.

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Published, JBC Papers in Press, September 4, 2001, DOI 10.1074/jbc.M105823200

*

This work was supported by grants from the Swedish Cancer Foundation and the Swedish Research Council (to G. v. H.) and by grants from the Swedish Research Council and the Swedish Foundation for International Cooperation in Research and Higher Education (to I. M. N.).The costs of publication of this article were defrayed in part by the payment of page charges. The article must therefore be hereby marked “advertisement” in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

Both authors supported by grants from the Academy of Finland, the Sigfrid Juselius Foundation, the Borg Foundation, the Magnus Ehrnrooth Foundation, the Walter and Lisi Wahl Foundation, the Medicinska Understödsföreningen Liv och Hälsa Foundation, and from the Åbo Akademi University.

**

Supported by National Institutes of Health Grant GM 26494 and by The Robert A. Welch Foundation.