Search PubMed⌕ Search

SEARCH · Search PubMed

Results for “Caveolae”

Search indexed PubMed citations on genomics, clinical trials, systematic reviews and public health. Explore titles, authors and supplied subject terms, then open the PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 163 records · Page 9Linked to original sources
PubMed2000

Cell biology of caveolae and its implication for clinical medicine.

Caveolae are small invaginations of the plasma membrane found in many cell types, and caveolins are integral membrane proteins that form the framework of caveolae. In the past several years, research on caveolae has developed explosively, and caveolae and/or caveolins have been shown to play many important roles in cell physiology: in particular, they are thought to be related to signal transduction, cholesterol transport, endocytosis and tumor suppression. On the other hand, some studies have suggested that another membrane domain called rafts is also involved in the same processes, and some confusion remains concerning the relationship between these two domains. Abnormalities in caveolae and/or caveolins have been found in various diseases, including cancer, atherosclerosis, muscular dystrophy and the Alzheimer's disease, which may make this domain a new focus for pharmacological research. This review will focus on the cell biology of caveolae, caveolins and rafts, and then summarize the implications of these findings for clinical studies.

Animals↗
PubMed1990

Three-dimensional observation on sarcoplasmic reticulum and caveolae in myocardium of spontaneously hypertensive rats.

Three-dimensional observation of intracellular membranous structures in myocardium was carried out in spontaneously hypertensive rats (SHR; a model of hypertrophied myocardium) under a scanning electron microscope (SEM) and compared with those of age- and sex-matched normotensive Wistar-Kyoto rats (WKY). There was no apparent difference in the ultrastructures of the myocardium between 5-week-old SHR (before the onset of hypertension but with mild cardiac hypertrophy) and age- and sex-matched control rats. Ten-week-old SHR in an early stage of hypertension with significant cardiac hypertrophy, showed a significant increase in the number of caveolae compared with those of 10-week-old WKY, and numerous abnormal caveolae aggregates connected by filamentous structures. Moreover the density of the network of sarcoplasmic reticulum (SR) was also increased, and some SR had a giant, squamous appearance. Accumulation of mitochondria with dense cristae was also observed in 10-week-old SHR. In 20-week-old SHR with established hypertension and cardiac hypertrophy, the caveolae and SR observed in 10-week-old SHR were no longer present, but caveolae were distributed in bands with variable width, parallel to the long axis of the myocardium. A wavy arrangement of mitochondria, fragmentation and stacks of mitochondrial cristae were observed in 20-week-old SHR. The changes of caveolae and giant squamous SR in cardiac hypertrophy observed in the present study have never been reported in previous studies. Our results suggest that the changes in caveolae, SR and mitochondria observed in SHR may be important morphological signs during development of cardiac hypertrophy in SHR.

Animals↗
PubMed1997

Expression of caveolae on the surface of rat arterial smooth muscle cells is dependent on the phenotypic state of the cells.

Both after vascular injury and when established in vitro, arterial smooth muscle cells pass through a characteristic change in phenotype. This process includes a prominent structural reorganization with partial loss of myofilaments and formation of a large endoplasmic reticulum and Golgi complex. As a result, the cells lose their contractility and become able instead to divide and to secrete extracellular matrix components. In the present study, the expression of plasma membrane caveolae in rat arterial smooth muscle cells was studied in primary culture and during the formation of neointimal thickenings after balloon injury. Electron microscopic analysis revealed that the number of caveolae (identified as flask-shaped invaginations of the plasma membrane) was reduced when the cells converted from a contractile to a synthetic phenotype (as defined morphologically) and then increased again when they readopted a more differentiated state. However, immunoblotting analysis did not show any changes in the cellular content of caveolin (a major protein component of caveolae) during the 1st week in culture. At the same time, immunocytochemical staining demonstrated a shift in the localization of caveolin from small spot-like structures dispersed over the cell surface to vesicular structures in the perinuclear cytoplasm. These findings indicate that the transition of smooth muscle cells from a contractile to a synthetic phenotype involves a marked decline in the number of plasma membrane caveolae. In parallel, caveolin is internalized and redistributed to Golgi-associated vesicles in the perinuclear cytoplasm. In context of the rapidly increasing awareness of the importance of caveolae both in signal transduction and intracellular cholesterol transport, it seems likely that the variations in the number of caveolae may be significant for the functional differences between smooth muscle cells in different phenotypes.

Animals↗
PubMed1998

Early effects of pp60(v-src) kinase activation on caveolae.

Members of the nonreceptor tyrosine kinase family appear to be targeted to caveolae membrane. We have used a Rat-1 cell expressing a temperature sensitive pp60(v-src) kinase to assess the initial changes that take place in caveolae after kinase activation. Within 24-48 h after cells were shifted to the permissive temperature, a set of caveolae-specific proteins became phosphorylated on tyrosine. During this period there was a decline in the caveolae marker protein, caveolin-1, a loss of invaginated caveolae, and a 70% decline in the sphingomyelin content of the cell. One of the phosphorylated proteins was caveolin-1 but it was associated in coimmunoprecipitation assays with both a 30 kDa and a 27 kDa tyrosine-phosphorylated protein. Finally, the cells changed from having a typical fibroblast morphology to a rounded shape lacking polarity. In light of the recent evidence that diverse signaling events originate from caveolae, pp60(v-src) kinase appears to cause global changes to this membrane domain that might directly contribute to the transformed phenotype.

Animals↗
PubMed2001

Caveolae and their coat proteins, the caveolins: from electron microscopic novelty to biological launching pad.

Caveolins are a family of proteins that coat the cytoplasmic face of caveolae, vesicular invaginations of the plasma membrane. These proteins are central to the organization of the proteins and lipids that reside in caveolae. Caveolins transport cholestrol to and from caveolae, and they regulate the activity of signaling proteins that reside in caveolae. Studying the genes encoding the caveolae coat proteins, we have learned much about how they perform these multiple functions.

Animals↗
PubMed2001

Caveolae and the organization of carbohydrate metabolism in vascular smooth muscle.

We have previously found that glycolysis and gluconeogenesis occur in separate "compartments" of the VSM cell. These compartments may result from spatial separation of glycolytic and gluconeogenic enzymes (Lloyd and Hardin [1999] Am J Physiol Cell Physiol. 277:C1250-C1262). We have also found that an intact plasma membrane is essential for compartmentation to exist (Lloyd and Hardin [2000] Am J Physiol Cell Physiol. 278:C803-C811), suggesting that glycolysis and gluconeogenesis may be associated with distinct plasma membrane microdomains. Caveolae are one such microdomain, in which proteins of related function colocalize. Thus, we hypothesized that membrane-associated glycolysis occurs in association with caveolae, while gluconeogenesis is localized to non-caveolae domains. To test this hypothesis, we disrupted caveolae in vascular smooth muscle (VSM) of pig cerebral microvessels (PCMV) with beta methyl-cyclodextrin (CD) and examined the metabolism of [2-(13)C]glucose (a glycolytic substrate) and [1-(13)C]fructose 1,6-bisphosphate (FBP, a gluconeogenic substrate in PCMV) using (13)C nuclear magnetic resonance spectroscopy. Caveolar disruption reduced flux of [2-(13)C]glucose to [2-(13)C]lactate, suggesting that caveolar disruption partially disrupted the glycolytic pathway. Caveolae disruption may also have resulted in a breakdown of compartmentation, since conversion of [1-(13)C]FBP to [3-(13)C]lactate was increased by CD treatment. Alternatively, the increased [3-(13)C]lactate production may reflect changes in FBP uptake, since conversion of [1-(13)C]FBP to [3-(13)C]glucose was also elevated in CD-treated cells. Thus, a link between caveolar organization and metabolic organization may exist.

Animals↗
PubMed2002

Structure and function of endothelial caveolae.

Caveolae are spherical invaginations of the plasma membrane and associated vesicles that are found at high surface densities in most cells, endothelia included. Their structural framework has been shown to consist of oligomerized caveolin molecules interacting with cholesterol and sphingolipids. Caveolae have been involved in many cellular functions such as endocytosis, signal transduction, mechano-transduction, potocytosis, and cholesterol trafficking. Some confusion still persists in the field with respect to the relationship between caveolae and the lipid rafts, which have been involved in many of the above functions. In addition to all these, endothelial caveolae have been involved in capillary permeability by their participation in the process of transcytosis. This short review will focus on their structure and components, methods used to determine these components, and the role of caveolae in the transendothelial exchanges between blood plasma and the interstitial fluid.

Animals↗
PubMed2006

Modelling the effect of caveolae on G-protein activation.

In this paper, we study the effects on G-protein activation of a non-uniform distribution of signalling components. The spatial heterogeneity is attributed to caveolae, a specific membrane microdomain which has been observed to redistribute and concentrate signalling molecules. Diffusive coagulation-fragmentation equations are used to describe the aggregation of caveolin homo-oligomers and the subsequent formation of caveolae. A system of reaction-diffusion equation is thus formulated and, in order to describe the restrictions imposed by caveolae on the movement of receptors and G-protein, a segregation coefficient is introduced which serves to regulate the preference of the species to segregate according to the concentration of caveolae. The results demonstrate that the heterogeneous distribution of the signalling components and the efficiency of G-protein activation can vary significantly, depending on the concentration of caveolae.

Caveolae↗
PubMed2005

Structure of caveolae.

The introduction of the electron microscope to the study of the biological materials in the second half of the last century has dramatically expanded our view and understanding of the inner workings of cells by enabling the discovery and study of subcellular organelles. A population of flask-shaped or spherical invaginations of the plasma membrane were described and named plasmalemmal vesicles or caveolae. Until the discovery of caveolin-1 as their first molecular marker in early 1990s, the study of caveolae was the exclusive domain of electron microscopists that demonstrated caveolae at different surface densities in most mammalian cells with few exceptions. Electron microscopy techniques in combination with other approaches have also revealed the structural features of caveolae as well as some of their protein and lipid residents. This review summarizes the data on the structure and components of caveolae and their stomatal diaphragms.

Animals↗
PubMed2002

Caveolin-1/3 double-knockout mice are viable, but lack both muscle and non-muscle caveolae, and develop a severe cardiomyopathic phenotype.

The caveolin gene family consists of caveolins 1, 2, and 3. Caveolins 1 and 2 are co-expressed in many cell types, such as endothelial cells, fibroblasts, smooth muscle cells and adipocytes, where they form a heteroligomeric complex. In contrast, the expression of caveolin-3 is muscle-specific. Thus, the expression of caveolin-1 is required for caveolae formation in non-muscle cells, while the expression of caveolin-3 drives caveolae formation in striated muscle cell types (cardiac and skeletal). To create a truly caveolae-deficient mouse, we interbred Cav-1 null mice and Cav-3 null mice to generate Cav-1/Cav-3 double-knockout (Cav-1/3 dKO) mice. Here, we report that Cav-1/3 dKO mice are viable and fertile, despite the fact that they lack morphologically identifiable caveolae in endothelia, adipocytes, smooth muscle cells, skeletal muscle fibers, and cardiac myocytes. We also show that these mice are deficient in all three caveolin gene products, as caveolin-2 is unstable in the absence of caveolin-1. Interestingly, Cav-1/3 dKO mice develop a severe cardiomyopathy. At 2 months of age, analysis of Cav-1/3 dKO hearts via gated magnetic resonance imaging reveals a dramatic increase in left ventricular wall thickness, as compared with Cav-1-KO, Cav-3 KO, and wild-type mice. Further functional analysis of Cav-1/3 dKO hearts via transthoracic echocardiography demonstrates hypertrophy and dilation of the left ventricle, with a significant decrease in fractional shortening. As predicted, Northern analysis of RNA derived from the left ventricle of Cav-1/3 dKO mice shows a dramatic up-regulation of the atrial natriuretic factor message, a well-established biochemical marker of cardiac hypertrophy. Finally, histological analysis of Cav-1/3 dKO hearts reveals hypertrophy, disorganization, and degeneration of the cardiac myocytes, as well as chronic interstitial fibrosis and inflammation. Thus, dual ablation of both Cav-1 and Cav-3 genes in mice leads to a pleiotropic defect in caveolae formation and severe cardiomyopathy.

Adipocytes↗
PubMed2003

Association of the low-density lipoprotein receptor with caveolae in hamster and rat liver.

The association of the low-density lipoprotein (LDL) receptor with detergent resistant hepatic membranes was investigated using discontinuous sucrose gradients. In liver homogenates from both hamsters and rats, the fractions with the highest concentrations of LDL receptor coincided with the location of caveolin-1, a marker of the cholesterol-rich caveolae. Feeding the animals diets enriched in cholesterol slightly shifted both LDL receptor and caveolin-1 to positions of lower density. The cholesterol content of the caveolae fractions was increased 2-fold in animals fed cholesterol-supplemented diets. In homogenates of CHO cells, fractionated in the same manner, the LDL receptor was absent from the caveolae fractions but was present in denser fractions near the bottom of the gradient. Addition of caveolin-1 antibody to solubilized caveolae from liver coimmunoprecipitated the LDL receptor. These observations suggest that in liver, the LDL receptor is mainly located in caveolae. This location contrasts with the clathrin-coated pit location observed in fibroblasts and CHO cells.

Animals↗
PubMed2001

The caveolin triad: caveolae biogenesis, cholesterol trafficking, and signal transduction.

Caveolins are a family of proteins that coat the cytoplasmic face of caveolae, vesicular invaginations of the plasma membrane. These proteins are central to the organization of the proteins and lipids that reside in caveolae. Caveolins transport cholesterol to and from caveolae, and they regulate the activity of signaling proteins that reside in caveolae. Through studying the genes encoding the caveolae coat proteins, we have learned much about how they perform these multiple functions.

Amino Acid Sequence↗
PubMed2000

Cholesterol and caveolae: structural and functional relationships.

Caveolae are free cholesterol (FC)- and sphingolipid-rich surface microdomains abundant in most peripheral cells. Caveolin, a FC binding protein, is a major structural element of these domains. Caveolae serve as portals to regulate cellular FC homeostasis, possibly via their association with ancillary proteins including scavenger receptor B1. The FC content of caveolae regulates the transmission of both extracellular receptor-mediated and endogenous signal transduction via changes in the composition of caveolin-associated complexes of signaling intermediates. By controlling surface FC content, reporting membrane changes by signal transduction to the nucleus, and regulating signal traffic in response to extracellular stimuli, caveolae exert a multifaceted influence on cell physiology including growth and cell division, adhesion, and hormonal response. Cell surface lipid 'rafts' may assume many of the functions of caveolae in cells with low levels of caveolin.

Animals↗
PubMed2001

Co-option of endocytic functions of cellular caveolae by pathogens.

It is increasingly becoming clear that various immune cells are infected by the very pathogens that they are supposed to attack. Although many mechanisms for microbial entry exist, it appears that a common route of entry shared by certain bacteria, viruses and parasites involves cellular lipid-rich microdomains sometimes called caveolae. These cellular entities, which are characterized by their preferential accumulation of glycosylphosphatidylinositol (GPI)-anchored molecules, cholesterol and various glycolipids, and a distinct protein (caveolin), are present in many effector cells of the immune system including neutrophils, macrophages, mast cells and dendritic cells. These structures have an innate capacity to endocytoze various ligands and traffic them to different intracellular sites and sometimes, back to the extracellular cell surface. Because caveolae do not typically fuse with lysosomes, the ligands borne by caveolar vesicles are essentially intact, which is in marked contrast to ligands endocytozed via the classical endosome-lysosome pathway. A number of microbes or their exotoxins co-opt the unique features of caveolae to enter and traffic, without any apparent loss of viability and function, to different sites within immune and other host cells. In spite of their wide disparity in size and other structural attributes, we predict that a common feature among caveolae-utilizing pathogens and toxins is that their cognate receptor(s) are localized within plasmalemmal caveolae of the host cell.

Adhesins, Bacterial↗
PubMed2001

Distinction between signaling mechanisms in lipid rafts vs. caveolae.

The relative importance of lipid rafts vs. specialized rafts termed caveolae to influence signal transduction is not known. Here we show that in cells lacking caveolae, the dually acylated protein, endothelial nitric oxide synthase (eNOS), localizes to cholesterol-rich lipid raft domains of the plasma membrane. In these cells, expression of caveolin-1 (cav-1) stimulates caveolae biogenesis, promotes the interaction of cav-1 with eNOS, and the inhibition of NO release from cells. Interestingly, in cells where cav-1 does not drive caveolae assembly, despite equal levels of cav-1 and eNOS and localization of both proteins to raft domains of the plasmalemma, the physical interaction of eNOS with cav-1 is dramatically less resulting in less inhibition of NO release. Thus, cav-1 concentrated in caveolae, not in rafts, is in closer proximity to eNOS and is necessary for negative regulation of eNOS function, thereby providing the first clear example of spatial regulation of signaling in this organelle that is distinct from raft domains.

Animals↗
PubMed2001

Caveolae-deficient endothelial cells show defects in the uptake and transport of albumin in vivo.

The role of endothelial cell caveolae in the uptake and transport of macromolecules from the blood-space to the tissue-space remains controversial. To address this issue directly, we employed caveolin-1 gene knock-out mice that lack caveolin-1 protein expression and caveolae organelles. Here, we show that endothelial cell caveolae are required for the efficient uptake and transport of a known caveolar ligand, i.e. albumin, in vivo. Caveolin-1-null mice were perfused with 5-nm gold-conjugated albumin, and its uptake was followed by transmission electron microscopy. Our results indicate that gold-conjugated albumin is not endocytosed by Cav-1-deficient lung endothelial cells and remains in the blood vessel lumen; in contrast, gold-conjugated albumin was concentrated and internalized by lung endothelial cell caveolae in wild-type mice, as expected. To quantitate this defect in uptake, we next studied the endocytosis of radioiodinated albumin using aortic ring segments from wild-type and Cav-1-null mice. Interestingly, little or no uptake of radioiodinated albumin was observed in the aortic segments from Cav-1-deficient mice, whereas aortic segments from wild-type mice showed robust uptake that was time- and temperature-dependent and competed by unlabeled albumin. We conclude that endothelial cell caveolae are required for the efficient uptake and transport of albumin from the blood to the interstitium.

Albumins↗
PubMed2001

Cholesteryl ester is transported from caveolae to internal membranes as part of a caveolin-annexin II lipid-protein complex.

We previously demonstrated that in Chinese hamster ovary cells scavenger receptor, class B, type I-dependent selective cholesteryl ester uptake occurs in caveolae. In the present study we hypothesized that cholesteryl ester is transported from caveolae through the cytosol to an internal membrane by a caveolin chaperone complex similar to the one we originally described for the transport of newly synthesized cholesterol. To test this hypothesis we incubated Chinese hamster ovary cells expressing scavenger receptor, class B, type I with [(3)H]cholesteryl ester-labeled high density lipoprotein, subfractionated the cells and looked for a cytosolic pool of [(3)H]cholesteryl ester. The radiolabeled sterol initially appeared in the caveolae fraction, then in the cytosol, and finally in the internal membrane fraction. Caveolin IgG precipitated all of the [(3)H]cholesteryl ester associated with the cytosol. Co-immunoprecipitation studies demonstrated that in the presence of high density lipoprotein, but not low density lipoprotein or lipoprotein-deficient serum, caveolin IgG precipitated four proteins: annexin II, cyclophilin 40, caveolin, and cyclophilin A. Caveolin acylation-deficient mutants were used to demonstrate that acylation of cysteine 133 but not cysteine 143 or 156 is required for annexin II association with caveolin and the rapid transport of cholesteryl esters out of caveolae. We conclude that a caveolin-annexin II lipid-protein complex facilitates the rapid internalization of cholesteryl esters from caveolae.

Animals↗
PubMed2002

A molecular sensor detects signal transduction from caveolae in living cells.

Biochemical and cell fractionation studies suggest caveolae contain functionally organized sets of signaling molecules that are capable of transmitting specific signals to the cell. It is not known, however, whether any signals actually originate from caveolae in living cells. To address this question, we have engineered the calcium sensor yellow cameleon so that it is targeted either to the plasma membrane, caveolae, or the cytoplasm of endothelial cells. Quantitative measurements of the three Ca2+ pools detected by these probes indicate that caveolae are preferred sites of Ca2+ entry when Ca2+ stores in the endoplasmic reticulum are depleted. These results suggest that the signaling machinery in control of Ca2+ entry is functionally organized in the caveolae of living cells.

Animals↗