Dynamic and Regulated Association of Caveolin with Lipid Bodies: Modulation of Lipid Body Motility and Function by a Dominant Negative Mutant

Abstract

Caveolins are a crucial component of caveolae but have also been localized to the Golgi complex, and, under some experimental conditions, to lipid bodies (LBs). The physiological relevance and dynamics of LB association remain unclear. We now show that endogenous caveolin-1 and caveolin-2 redistribute to LBs in lipid loaded A431 and FRT cells. Association with LBs is regulated and reversible; removal of fatty acids causes caveolin to rapidly leave the lipid body. We also show by subcellular fractionation, light and electron microscopy that during the first hours of liver regeneration, caveolins show a dramatic redistribution from the cell surface to the newly formed LBs. At later stages of the regeneration process (when LBs are still abundant), the levels of caveolins in LBs decrease dramatically. As a model system to study association of caveolins with LBs we have used brefeldin A (BFA). BFA causes rapid redistribution of endogenous caveolins to LBs and this association was reversed upon BFA washout. Finally, we have used a dominant negative LB-associated caveolin mutant (cav DGV ) to study LB formation and to examine its effect on LB function. We now show that the cav DGV mutant inhibits microtubule-dependent LB motility and blocks the reversal of lipid accumulation in LBs.

Caveolin-1 inhibits breast cancer growth and metastasis

“…The actin cytoskeleton, as revealed by phalloidin staining, showed partial colocalization with caveolin-1 in clones 7 and 9 ( Figure 1c). Caveolin-1 did not colocalize with lipid droplets as assessed by Oil Red O staining (data not shown), in contrast to reports in other cell types (Ostermeyer et al, 2001;Pol et al, 2004).…”

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

“…Pol et al 24 reported an important increase and redistribution of Cav-1 from the cell surface to the newly formed lipid bodies in liver regeneration after PH. These authors suggested that this association of Cav-1 with lipid bodies is due to the lipid mobilization process together with the arrest of endocytosis and membrane trafficking that accounts for regenerating liver.…”

“…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.…”

Raft association and lipid droplet targeting of flotillins are independent of caveolin

“…However, this study showed that flotillins were not recruited to lipid bodies, but the authors used a flotillin-2-myc fusion construct to study the targeting of flotillins to lipid droplets, consistent with our finding that flotillin-2 remains unassociated with lipid bodies upon OA treatment. Interestingly, an increasing number of studies have revealed that caveolins can redistribute to lipid droplets under various conditions, including OA treatment (Fujimoto et al, 2001;Ostermeyer et al, 2001;Pol et al, 2001Pol et al, , 2004Brasaemle et al, 2004). This lipid-body targeting of caveolins is thought to regulate cellular lipid balance, especially cellular cholesterol homeostasis Pol et al, 2005;Le Lay et al, 2006).…”

“…In particular, it was recently described that caveolins can move from the plasma membrane to lipid bodies in response to oleic acid treatment (Pol et al, 2001(Pol et al, , 2004. In addition, flotillin-1 has been found in purified lipid droplets formed after fatty acid loading in CHO cells (Liu et al, 2004).…”