Amyloid beta-protein stimulates trafficking of cholesterol and caveolin-1 from the plasma membrane to the Golgi complex in mouse primary astrocytes.
The Golgi complex plays a key role in cholesterol trafficking in cells. Our earlier study demonstrated amyloid beta-protein (Abeta) alters cholesterol distribution and abundance in the Golgi complex of astrocytes. We now test the hypothesis that the Abeta-induced increase in Golgi complex cholesterol is due to retrograde movement of the cholesterol carrier protein caveolin-1 from the cell plasma membrane to the Golgi complex in astrocytes. Results with mouse primary astrocytes indicated that Abeta(1-42)-induced increase in cholesterol and caveolin abundance in the Golgi complex was accompanied by a reduction in cholesterol and caveolin levels in the plasma membrane. Transfected rat astrocytes (DITNC1) with siRNA directed at caveolin-1 mRNA inhibited the Abeta(1-42)-induced redistribution of both cholesterol and caveolin from the plasma membrane to the Golgi complex. In astrocytes not treated with Abeta(1-42), suppression of caveolin-1 expression also significantly reduced cholesterol abundance in the Golgi complex, further demonstrating the role for caveolin in retrograde transport of cholesterol from the plasma membrane to the Golgi complex. Perturbation of this process by Abeta(1-42) could have consequences on membrane structure and cellular functions requiring optimal levels of cholesterol.
Igbavboa
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Department of Pharmacology, University of Minnesota School of Medicine and Geriatric Research, Education and Clinical Center, VA Medical Center, 6-120 Jackson Hall, 321 Church Street Southeast, Minneapolis, MN 55455, USA. igbav001@umn.edu
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Weisman
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D016229:Amyloid beta-Peptides / Q000494:pharmacology / Q000502:physiology*; D000818:Animals; D001253:Astrocytes / Q000378:metabolism*; D001692:Biological Transport; D051242:Caveolin 1 / Q000235:genetics / Q000378:metabolism*; D002462:Cell Membrane / Q000378:metabolism*; D002478:Cells, Cultured; D002784:Cholesterol / Q000378:metabolism*; D055785:Gene Knockdown Techniques; D006056:Golgi Apparatus / Q000378:metabolism*; D051379:Mice; D008810:Mice, Inbred C57BL; D010446:Peptide Fragments / Q000494:pharmacology; D021381:Protein Transport; D034741:RNA, Small Interfering / Q000235:genetics; D051381:Rats
D016229:Amyloid beta-Peptides; D051242:Caveolin 1; D010446:Peptide Fragments; D034741:RNA, Small Interfering; C075222:amyloid beta-protein (1-42); D002784:Cholesterol