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J. Biol. Chem., Vol. 276, Issue 45, 41748-41754, November 9, 2001
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From the 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.
Inhibition of Protein Translocation across the Endoplasmic
Reticulum Membrane by Sterols*
§,
,,
Department of Biochemistry and Biophysics,
Stockholm University, SE-106 91 Stockholm, Sweden, the
¶ Department of Biochemistry and Pharmacy, Åbo Akademi
University, P. O. Box 66, FIN-20521 Turku, Finland, and the
§ Department of Medical Biochemistry and Genetics, Texas
A & M University System Health Science Center, College
Station, Texas 77843-1114
*
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.
To whom correspondence should be addressed. Tel.:
46-8-16-25-90; Fax: 46-8-15-36-79; E-mail:
gunnar@dbb.su.se.
Copyright © 2001 by The American Society for Biochemistry and Molecular Biology, Inc.
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