Caveolae Cholesterol and Caveolin Localization to Caveolae

Soon after caveolin was first cloned, studies with filipin - an antibiotic that specifically binds cholesterol [41-43] showed that filipin-cholesterol complexes were enriched in nonclathrin-coated endosomes and regions of membrane corresponding to caveolae. This raised the question of how and why cholesterol was enriched in caveolae. Experimental manipulation of caveolae cholesterol by the addition of bacterial cholesterol oxidase to the media of cells was used to investigate this question [6,44]. Cholesterol oxidase caused rapid oxidation of cholesterol in caveolae, leading to cholesterol dispersal and the rapid internalization of caveolin-1 [6]. The removal of cholesterol oxidase from the media allowed the re-formation of caveolae, and both caveolin-1 and cholesterol were restored to caveolae in the plasma membrane over a period of about 90 minutes. Immunolocalization studies showed that caveolin-1 moved rapidly out of the caveolae, and was subsequently found on vesicles in the endoplasmic reticulum-Golgi-intermediate-compartment (ER-GIC), a region between the Golgi and the endoplasmic reticulum (ER) [6]. This identified a very rapid pathway connecting the plasma membrane to a region adjacent to the ER, as caveolin totally redistributed within 30 seconds following the addition of bacterial cholesterol oxidase. Temperature shifting and inhibitors were employed to define a cycle of caveolin-1 movement from cell-surface caveolae into the cell and back to the cell surface. Caveolin-1 rapidly translocated first to the rough ER (within 30 seconds), then slowly over 15-20 minutes to the ER-GIC, to the Golgi, before finally returning to surface caveolae. An investigation of choles terol changes during the same time course showed that cholesterol followed a similar pattern of movement out of the caveolae, followed by a slow return to the caveolae, suggesting that caveolin-1 and cholesterol were linked together in a cycle. These studies were among the first to reveal a caveolin-trafficking cycle between cell-surface caveolae and the ER-Golgi membranes, for the transport of both cav-eolin and cholesterol between the plasma membrane and these perinuclear organelles.

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Essentials of Human Physiology

Essentials of Human Physiology

This ebook provides an introductory explanation of the workings of the human body, with an effort to draw connections between the body systems and explain their interdependencies. A framework for the book is homeostasis and how the body maintains balance within each system. This is intended as a first introduction to physiology for a college-level course.

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