Caveolin, Cholesterol, and Lipid Droplets?

Abstract

Caveolins constitute the coat of caveolae, specialized domains of the plasma membrane. A large body of evidence suggests that caveolae are enriched in sphingolipids and cholesterol. Besides a role in signal transduction and in the sorting of membrane components, a diverse range of functions has been assigned to the caveolins in the cellular homeostasis of cholesterol. Cholesterol is essential for numerous membrane processes, and its concentration in the cell is governed by a delicate sensor-effector mechanism. However, the basic rules that govern the distribution and dynamics of cholesterol in cells are not understood, a situation that may be changed by an improved insight in the actions of cholesterol-binding proteins like caveolins. Three papers in the present issue report unexpectedly that caveolins can be found on the surface of cytoplasmic lipid droplets (Fujimoto et al., 2001;Ostermeyer et al., 2001;Pol et al., 2001). Lipid droplets consist of apolar lipids and are thought to serve as inert energy storage sites. Caveolin transport to the lipid droplets may represent an "overflow" pathway from the ER under conditions where their concentration in the ER is enhanced (Ostermeyer et al., 2001). More sensational proposals are that caveolin on lipid droplets is a key component in maintaining the cellular cholesterol balance (Pol et al., 2001) and that caveolin populates a raft-like membrane domain on the droplet surface that is involved in intracellular signaling (Fujimoto et al., 2001).

Association of Stomatin with Lipid Bodies

“…Similar to the caveolins, it is apparently the overexpression of stomatin that targets this protein to the LBs. In other words, the transport of highly expressed caveolins or stomatin to the LBs may represent an "overflow" pathway from the ER (16). The formation of LBs and the co-localization of endogenous stomatin additionally depend on the availability of fatty acids.…”

“…LBs are found in most eukaryotic cells and play a role in the storage and turnover of neutral lipids, notably triacylglycerol, cholesteryl ester, and retinyl ester, depending on the cell type (15)(16)(17)(18). They are thought to originate from the membrane of the ER with newly synthesized neutral lipids being inserted between the bilayer causing the cytoplasmic leaflet to bulge and eventually bud off into the cytoplasm.…”

Involvement of ACSL in local synthesis of neutral lipids in cytoplasmic lipid droplets in human hepatocyte HuH7

“…A major hypothesis accounting for LD formation is that LDs originate from the accumulation of neutral lipids in ER membranes. The synthesis of neutral lipids leads to their accumulation in a space between the leaflets of the membranous bilayers of the ER, with subsequent budding off of LDs from it (14,(40)(41)(42). A part of proteins identified in LDs may be transferred from ER membranes to LDs in the course of LD formation.…”

Caveolin-1/3 Double-Knockout Mice Are Viable, but Lack Both Muscle and Non-Muscle Caveolae, and Develop a Severe Cardiomyopathic Phenotype

“…8,9 Initially considered to be mere conduits for endocytosis, caveolae are now recognized to have pleiotropic effects on numerous cellular events. Caveolin family members have been proposed to participate in vesicular trafficking , 10 lipid metabolism , 11,12 and various signal transduction processes. The "caveolae signaling hypothesis" states that caveolae serve as an integrated platform to concentrate and modulate the activity of specific lipidmodified signaling molecules, including Src family tyrosine kinases, H-Ras, eNOS, and heterotrimeric G proteins.…”