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Volume 272, Number 31,
Issue of August 1, 1997
pp. 19242-19247
©1997 by The American Society for Biochemistry and Molecular Biology, Inc.
Signal Transduction via Glycosyl Phosphatidylinositol-anchored
Proteins in T Cells Is Inhibited by Lowering Cellular Cholesterol
(Received for publication, April 22, 1997, and in revised form, May 28, 1997)
Thomas M.
Stulnig
,
Markus
Berger
,
Thomas
Sigmund
,
Hannes
Stockinger
¶
,
Václav
Ho ej í
and
Werner
Waldhäusl
From the Department of Internal Medicine III,
University of Vienna, Währinger Gürtel 18-20, A-1090
Vienna, Austria, ¶ Institute of Immunology, Vienna International
Research Cooperation Center, University of Vienna, Brunnerstrasse 59, A-1235 Vienna, Austria and Institute of Molecular Genetics,
Academy of Sciences of the Czech Republic, Víde ská
1083, 14220 Prague 4, Czech Republic
Glycosylphosphatidylinositol (GPI)-anchored
proteins can deliver costimulatory signals to lymphocytes, but the
exact pathway of signal transduction involved is not yet characterized.
GPI-anchored proteins are fixed to the cell surface solely by a
phospholipid moiety and are clustered in distinct membrane domains that
are formed by an unique lipid composition requiring cholesterol. To elucidate the role of membrane lipids for signal transduction via
GPI-anchored proteins, we studied the influence of reduced cellular
cholesterol content on calcium signaling via GPI-anchored CD59
and CD48 in Jurkat T cells. Lowering cholesterol by different inhibitors of cellular cholesterol synthesis suppressed calcium response via GPI-anchored proteins by about 50%, whereas stimulation via CD3 was only minimally affected (<10%). The decrease in overall calcium response via GPI-anchored proteins was reflected by inhibition of calcium release from intracellular stores. Cell surface expression of GPI-anchored proteins was not changed quantitatively by lowering cellular cholesterol, and neither was the pattern of immunofluorescence in microscopic examination. In addition, the distribution of
GPI-anchored proteins in detergent-insoluble complexes remained
unaltered. These results suggest that cellular cholesterol is an
important prerequisite for signal transduction via GPI-anchored
proteins beyond formation of membrane domains.

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Copyright © 1997 by the American Society for Biochemistry and Molecular Biology.
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