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Cholesterol Is Required for Efficient Endoplasmic Reticulum-to-Golgi Transport of Secretory Membrane Proteins

Ridsdale, Andrew, Denis, Maxime, Gougeon, Pierre-Yves, Ngsee, Johnny K., Presley, John F., Zha, Xiaohui·2006·Molecular Biology of the Cell
DOI 10.1091/mbc.e05-02-0100
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Abstract

Although cholesterol is synthesized in the endoplasmic reticulum (ER), compared with other cellular membranes, ER membrane has low cholesterol (3–6%). Most of the molecular machinery that regulates cellular cholesterol homeostasis also resides in the ER. Little is known about how cholesterol itself affects the ER membrane. Here, we demonstrate that acute cholesterol depletion in ER membranes impairs ER-to-Golgi transport of secretory membrane proteins. Cholesterol depletion is achieved by a brief inhibition of cholesterol synthesis with statins in cells grown in cholesterol-depleted medium. We provide evidence that secretory membrane proteins vesicular stomatitis virus glycoprotein and scavenger receptor A failed to be efficiently transported from the ER upon cholesterol depletion. Fluorescence photobleaching recovery experiments indicated that cholesterol depletion by statins leads to a severe loss of lateral mobility on the ER membrane of these transmembrane proteins, but not loss of mobility of proteins in the ER lumen. This impaired lateral mobility is correlated with impaired ER-to-Golgi transport. These results provide evidence for the first time that cholesterol is required in the ER membrane to maintain mobility of membrane proteins and thus protein secretion.

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  • After internalization, the acidic endosome induces conformational changes in LDLR, allowing dissociation from LDL; LDLR recycles to the hepatocyte surface while LDL cholesterol is trafficked to lysosomes for degradation.

    “Following internalization, the acidic environment of the endosome induces conformational changes in LDLR, allowing it to dissociate from LDL particles. LDLR is then recycled back to the hepatocyte surface, while LDL cholesterol is trafficked to lysosomes for degradation24–27.”

    From ABCC4 impairs the clearance of plasma LDL cholesterol through suppressing LDLR expression in the liver (2025) · cites this paper as [25]

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Metadata

Authors
Ridsdale, A., Denis, M., Gougeon, P.-Y., Ngsee, J. K., Presley, J. F., & Zha, X.
Venue
Molecular Biology of the Cell
Publisher
American Society for Cell Biology (ASCB)
Published
2006-04
Volume
17
Issue
4
Pages
1593-1605
ISSN
  • 1059-1524
  • 1939-4586
DOI
10.1091/mbc.e05-02-0100
Cited by
113
References
2
Language
en

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