Caveolae caveolin expression

Fujita T, Toya Y, Iwatsubo K, et al. Accumulation of molecules involved in ar adrenergic signal within caveolae caveolin expression and the development of cardiac hypertrophy. Cardiovasc Res 2001 51 709-716. 

In MDR cells, a significant fraction of P-gp is found associated with caveolin-rich membranes, and there is a substantial increase in the number of caveolae and caveolin-1 protein level. For example, both multidrug resistant human colon adenocarcinoma HT-29 cells and adriamycin-resistant breast adenocarcinoma MCF-7 cells display about a 12-fold increase in caveolin expression, which correlates with an approximate fivefold increase in morphologically identifiable caveolae [55], In addition, these cells exhibit increased amounts of phospholipase D and lipids such as cholesterol, glucosylceramide, and sphingomyelin [56, 57], Similarly, taxol-resistant A549 cells display both increased caveolin expression and caveolae numbers [58], While these correlations track with MDR, they do not suggest a simple mechanism for the role of... 

Carcinogenesis involves a complex series of genetic and biochemical events that enable transformed cells to proliferate, metastasize, migrate to secondary sites, and, sometimes, acquire resistance to chemotherapy. In Sect. 25.4.1, we will discuss how caveolin-1 expression correlates with cancerous growth, a potential mechanism of chemotherapy drug resistance, and how caveolae may be particularly exploited for cancer therapeutic strategies. 

J. R. Glenney Jr. and D. Soppet. Sequence and expression of caveolin, a protein component of caveolae plasma membrane domains phosphorylated on tyrosine in Rous sarcoma virus-transformed fibroblasts. Proc. Natl. Acad. Sci. USA 89 10517— 10521 (1992). 

It should be noted that the protein caveolin-1 is not necessarily an integral part of caveolae. The so-called lipid-raft mediated pathways have been studied mainly in cells that do not express caveolin-1. Apparently, these mechanisms are similar to caveolae uptake and are therefore discussed in the caveolae section. For detailed reviews on caveolae uptake, see Refs. (25-30). 

Probably the most appropriate marker for this pathway is caveolin-1 tagged with GFP, which after gene expression, is located at sites of caveolae as well as in the Golgi complex (20,26). 

In this chapter, we provide protocols to determine the ability of a peptide to mediate DNA internalization in cultured human tumor cells. Fluorescence-assisted cell sorting (FACS) analysis is used to obtain quantitative data on the time and temperature dependence of macromolecular delivery. Confocal microscopy is used to study the subcellular localization in both fixed and live cells. Fluorescently labeled transferrin and dextran are used to label the clathrin-dependent (15) and the non-clathrin, non-caveolar (16) endocytic compartments, respectively. Expression of a caveolin-l-YFP fusion protein is used to label cell surface caveolae and intracellular caveosomes (17). Finally a protocol, for the overexpression of dominant-negative dynamin [GTPase deficient dynamin-2 containing the amino acid substitution K44A (18)] is provided to evaluate the dynamin dependence of the uptake mechanism. 

These structures can even be induced to form in cells normally lacking caveolae by inducing the expression of caveolin... 

Fra AM, Williamson E, Simons K, Parton RG. De novo formation of caveolae in lymphocytes by expression of VlP21-caveolin. Proc. Natl. Acad. Sci. U.S.A. 1995 92 8655-8659. 

Campbell L, Hollins AJ, Al-Eid A et al (1999) Caveolin-1 expression and caveolae biogenesis during cell transdifferentiation in lung alveolar epithelial primary cultures. Biochem Biophys Res Commun 262(3) 744-751 Danto SI, Zabski SM, Crandall ED (1992) Reactivity of alveolar epithelial cells in primary culture with type I cell monoclonal antibodies. Am J Respir Cell Mol Biol 6(3) 296-306... 

Another heat shock protein-immunophilin chaperone complex is involved in the trafficking of cholesterol.124 A macromolecular complex consisting of FKBP52, caveolin (a 22 kDa protein that plays a role in regulating cholesterol concentration), CyPA, CyP-40, and cholesterol, transports newly synthesized cholesterol from the ER to caveolae. In cells expressing the complex, treatment with either CsA or rapamycin disrupted the complex and interfered with the rapid transport of cholesterol. 

The involvement of clathrin-coated pits in endocytosis of PrP is surprising, as GPI-anchored proteins like PrP " lack a cytoplasmic domain that could interact directly with adapter proteins and clathrin. Indeed, it has heen speculated that other GPI-anchored proteins are excluded from coated pits and are internalized via other surface invaginations called caveolae (Anderson, 1993). We find, however, that caveolae are not responsible for internalization of PrP " in neuronal cells, as these cells lack morphologically recognizable caveolae and do not express caveolin (Shyng etal., 1994). 

Caveolin (Cav), structural protein necessary and sufficient for the formation of caveolae. Cav-1 and Cav-3 are co-expressed in most cell types, including endothelial cells, epithelial cells, and fibroblasts, whereas Cav-3 are expressed by cardiomyocytes. However, smooth muscle cells express all three caveolins. It has been reported that administration of a cell-permeable Cav-1 prevents the development of monocrotaline-induced pulmonary hypertension and right ventricular hypertrophy [T. Okamoto et al., J. Biol. Chem. 1998, 273, 5419 J.-F. Jasmin et al.. Circulation 2006, 224, 912]. 

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