Caveolin-1 Is Essential for Liver Regeneration

Fernández, Manuel A.; Albor, Cecilia V.; Ingelmo-Torres, Mercedes; Nixon, Susan J.; Ferguson, Charles; Kurzchalia, Teymuras V.; Tebar, Francesc; Enrich, Carlos; Parton, Robert G.; Pol, Albert

doi:10.1126/science.1130773

Cited by 242 publications

(226 citation statements)

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“…Our data show that Cav-1 increases and translocates to noncaveolar fractions and is phosphorylated in Y 14 in the course of liver regeneration. However, it is clear that in this mouse strain, and in contrast to previous work using a different genetic background, 25 Cav-1 is dispensable for liver regeneration because Cav-1 KO animals survived and fully regenerated liver function and size after PH.…”

Section: Discussioncontrasting

confidence: 40%

“…25 Because this fact has been associated with an impaired regenerative response after PH in these mice, we investigated the time course of the lipid droplet accumulation in sections of the remnant liver after Nile red staining. As Fig 6A-C shows, both Cav-1 ϩ/ϩ and Cav-1 Ϫ/Ϫ mice exhibited an important accumulation of lipids at 12-48 hours after PH.…”

Section: ™™™™™™™™™™™™™™™™™™™™™™™™™™™™™™™™™™™™™™™™™™™™™™™™™™™™mentioning

confidence: 99%

“…In liver and in different hepatocyte cell lines, the expression of Cav has been demonstrated, 19,20 and the internalization of specific ligands through caveolae has been reported. [21][22][23] Recent reports have identified changes in the expression of Cav-1 in liver regeneration after partial hepatectomy (PH), a process in which Cav-1 seems to be essential, 24,25 in human cirrhotic liver, 26 and in hepatocellular carcinogenesis. 27 In this study, we have investigated the role of Cav-1 in liver regeneration after PH and in liver cell lines.…”

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Dispensability and dynamics of caveolin-1 during liver regeneration and in isolated hepatic cells

et al. 2007

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C aveolae were originally identified with an electron microscope as flask-shaped membrane invaginations on the surface of epithelial 1 and endothelial cells. 2 These plasmalemmal vesicles are enriched in sphingolipids, cholesterol, and caveolin (Cav), the major protein constituent of these structures. 3 Three Cavs have been identified in differentiated cells with specific patterns of distribution. Cav-1 and Cav-2 are found in adipocytes and endothelial cells, 4 whereas Cav-3 is selectively expressed in muscle cells. 5 Caveolae participate in many cellular processes, including vesicular transport, 6 cholesterol homeostasis, 7 regulation of signal transduction, 8 integrin signaling, 9 and cell growth. 10 Despite this, it is rather surprising that all Cav-null mice are viable, including the complete caveola-less mouse; however, the combined loss of Cav-1 and Cav-3 has profound effects on the cardiovascular function. 11 Caveolae have now been demonstrated to concentrate a wide variety of signaling molecules, including Src family tyrosine kinases, H-Ras, heterotrimeric G protein ␣ subunits, protein kinase C isoforms, and endothelial nitric oxide synthase (NOS; i.e., NOS-3). 12 Many signaling molecules directly interact with Cav-1 through a defined modular protein domain, which is known as the Cavscaffolding domain. The Cav-scaffolding domain has been shown to directly inhibit the activation of NOS-3, 13 epidermal growth factor receptor, 14 and c-neu 15 among other molecules. Moreover, Cav-1 is a potent inhibitor of proliferative pathways such as the Ras-p42/p44 MAP (mitogen activated protein kinase) kinase cascades. 16 Cav-1 expression negatively regulates cell cycle progression through a p53/p21-dependent pathway, 17 and several cellular oncoproteins down-regulate Cav-1 expression. 10

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confidence: 40%

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Dispensability and dynamics of caveolin-1 during liver regeneration and in isolated hepatic cells

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“…Mutations in caveolin-1 have also been shown to be associated with the rare lipodystrophies: Berardinelli-Seip congenital lipodystrophy (OMIM:269700) and an atypical partial lipodystrophy and hypertriglyceridemia (Cao et al, 2008;Kim et al, 2008a). Caveolin-1 is also required for liver regeneration (Fernandez et al, 2006;Frank and Lisanti, 2007).Caenorhabditis elegans has two caveolin genes; cav-1 and cav-2 (Tang et al, 1997). cav-1 has been implicated in meiotic progression in the germ line (Scheel et al, 1999) and in neurotransmission at the neuromuscular junction (Parker et al, 2007).…”

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Caveolin-2 Is Required for Apical Lipid Trafficking and Suppresses Basolateral Recycling Defects in the Intestine ofCaenorhabditis elegans

Parker

Walker

et al. 2009

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Caveolins are plasma membrane-associated proteins that colocalize with, and stabilize caveolae. Their functions remain unclear although they are known to be involved in specific events in cell signaling and endocytosis. Caenorhabditis elegans encodes two caveolin genes, cav-1 and cav-2. We show that cav-2 is expressed in the intestine where it is localized to the apical membrane and in intracellular bodies. Using the styryl dye FM4-64 and BODIPY-labeled lactosylceramide, we show that the intestinal cells of cav-2 animals are defective in the apical uptake of lipid markers. These results suggest parallels with the function of caveolins in lipid homeostasis in mammals. We also show that CAV-2 depletion suppresses the abnormal accumulation of vacuoles that result from defective basolateral recycling in rme-1 and rab-10 mutants. Analysis of fluorescent markers of basolateral endocytosis and recycling suggest that endocytosis is normal in cav-2 mutants and thus, that the suppression of basolateral recycling defects in cav-2 mutants is due to changes in intracellular trafficking pathways. Finally, cav-2 mutants also have abnormal trafficking of yolk proteins. Taken together, these data indicate that caveolin-2 is an integral component of the trafficking network in the intestinal cells of C. elegans. INTRODUCTIONCaveolae are 50 -100-nm invaginations located on the plasma membrane of many cell types (Anderson, 1998). They are enriched in lipid raft-associated molecules: cholesterol, sphingolipids, glycosphingolipids, and many signaling and receptor proteins. Although identified more than 50 years ago, their functions have remained elusive. However, they are known to play roles in specific cell-signaling processes, and it is clear that endocytosis through caveolae is an important clathrin-independent endocytic pathway (Parton and Richards, 2003;Parton and Simons, 2007). A range of molecules including glycosphingolipids, glycosylphosphatidylinositol (GPI)-anchored proteins, cholera toxin B, and SV40 virus have been shown to traffic through caveolaedependent endocytosis pathways (see Marsh and Helenius, 2006;Mayor and Pagano, 2007; Parton and Simons, 2007 for reviews).Caveolae require caveolin proteins for formation so that depletion of caveolins results in loss of morphologically detectable caveolae (Drab et al., 2001;Galbiati et al., 2001). Furthermore, introduction of caveolin into cells that do not produce caveolae stimulates caveolar biogenesis (Lipardi et al., 1998). The majority of caveolin appears to traffic to the plasma membrane and is relatively immobile; however, internal caveolin-containing structures, named caveosomes, have been visualized (Parton and Simons, 2007) and appear to be an integral part of the caveolin-dependent endocytic machinery (Nichols, 2003). Mammalian cells have three caveolin subtypes: caveolin 1 is widely expressed, but is found at particularly high levels in adipocytes, endothelial cells, and fibroblasts. Caveolin 2 interacts with caveolin 1, whereas caveolin 3 is expressed in myocytes ...

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Lipid droplets provide metabolic flexibility for cancer progression

Safi,

Menéndez,

Pol

2024

FEBS Letters

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A hallmark of cancer cells is their remarkable ability to efficiently adapt to favorable and hostile environments. Due to a unique metabolic flexibility, tumor cells can grow even in the absence of extracellular nutrients or in stressful scenarios. To achieve this, cancer cells need large amounts of lipids to build membranes, synthesize lipid‐derived molecules, and generate metabolic energy in the absence of other nutrients. Tumor cells potentiate strategies to obtain lipids from other cells, metabolic pathways to synthesize new lipids, and mechanisms for efficient storage, mobilization, and utilization of these lipids. Lipid droplets (LDs) are the organelles that collect and supply lipids in eukaryotes and it is increasingly recognized that the accumulation of LDs is a new hallmark of cancer cells. Furthermore, an active role of LD proteins in processes underlying tumorigenesis has been proposed. Here, by focusing on three major classes of LD‐resident proteins (perilipins, lipases, and acyl‐CoA synthetases), we provide an overview of the contribution of LDs to cancer progression and discuss the role of LD proteins during the proliferation, invasion, metastasis, apoptosis, and stemness of cancer cells.

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Caveolin-1 Is Essential for Liver Regeneration

Cited by 242 publications

References 15 publications

Dispensability and dynamics of caveolin-1 during liver regeneration and in isolated hepatic cells

Dispensability and dynamics of caveolin-1 during liver regeneration and in isolated hepatic cells

Caveolin-2 Is Required for Apical Lipid Trafficking and Suppresses Basolateral Recycling Defects in the Intestine ofCaenorhabditis elegans

Lipid droplets provide metabolic flexibility for cancer progression

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