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Cover  Caveolae are small (~60 nm), flask-shaped invaginations of the plasma membrane that are believed to play a role in diverse cell processes such as endocytosis and signal transduction (reviewed by Shaul and Anderson, Am. J. Physiol. 1998, 275, L843). They were first recognized by Palade on the plasma membrane of endothelial cells (J. Appl. Phys. 1953, 24, 1424), and named two years later by Yamada, who coined the term "caveola" (little cave) to describe "a small pocket, vesicle, cave, or recess communication with the outside of the cell" in gallbladder epithelium (J. Biophys. Biochem. Cytol. 1995, 1, 445). Although present in most cell types, caveolae are particularly abundant in endothelial cells, smooth muscle cells, and adipocytes. Early freeze-fracture studies first indicated that caveolae represent specialized cell surface microdomains, a notion that is now supported by a wealth of immunocytochemical and biochemical studies. Thus, in smooth muscle cells, caveolae are disposed in parallel bands of plasma membrane that contain a much higher density of intramembrane particles than the intervening regions (Orci and Perrelet; Science, 1973, 181, 868). In addition, using filipin as a cholesterol probe, characteristic filipin-sterol complexes were found to be selectively concentrated in the caveolae-rich plasma membrane bands but virtually absent in the intervening bands, suggesting that caveolae reside in cholesterol-rich membrane domains (Montesano; Nature, 1979, 280, 328). Although caveolae were initially considered to play a role exclusively in fluid-phase endocytosis, a seminal study challenged this view by showing that caveolae are involved in the binding and receptor-mediated internalization of cholera and tetanus toxins (Montesano et al., Nature 1982, 296, 651). As the cell surface receptors for these toxins are membrane gangliosides, these studies also provided the first clue of what is today a largely accepted notion, i.e. that caveolae are glycolipid-enriched plasma membrane domains.---Lelio Orci


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