Caveolin-1 and -2 constitute a framework of caveolae in nonmuscle cells. In the present study, we showed that caveolin-2, especially its β isoform, is targeted to the surface of lipid droplets (LD) by immunofluorescence and immunoelectron microscopy, and by subcellular fractionation. Brefeldin A treatment induced further accumulation of caveolin-2 along with caveolin-1 in LD. Analysis of mouse caveolin-2 deletion mutants revealed that the central hydrophobic domain (residues 87–119) and the NH2-terminal (residues 70–86) and COOH-terminal (residues 120–150) hydrophilic domains are all necessary for the localization in LD. The NH2- and COOH-terminal domains appeared to be related to membrane binding and exit from ER, respectively, implying that caveolin-2 is synthesized and transported to LD as a membrane protein. In conjunction with recent findings that LD contain unesterified cholesterol and raft proteins, the result implies that the LD surface may function as a membrane domain. It also suggests that LD is related to trafficking of lipid molecules mediated by caveolins.
A melt has greater volume than a silicate solid of the same composition. But this difference diminishes at high pressure, and the possibility that a melt sufficiently enriched in the heavy element iron might then become more dense than solids at the pressures in the interior of the Earth (and other terrestrial bodies) has long been a source of considerable speculation. The occurrence of such dense silicate melts in the Earth's lowermost mantle would carry important consequences for its physical and chemical evolution and could provide a unifying model for explaining a variety of observed features in the core-mantle boundary region. Recent theoretical calculations combined with estimates of iron partitioning between (Mg,Fe)SiO(3) perovskite and melt at shallower mantle conditions suggest that melt is more dense than solids at pressures in the Earth's deepest mantle, consistent with analysis of shockwave experiments. Here we extend measurements of iron partitioning over the entire mantle pressure range, and find a precipitous change at pressures greater than ∼76 GPa, resulting in strong iron enrichment in melts. Additional X-ray emission spectroscopy measurements on (Mg(0.95)Fe(0.05))SiO(3) glass indicate a spin collapse around 70 GPa, suggesting that the observed change in iron partitioning could be explained by a spin crossover of iron (from high-spin to low-spin) in silicate melt. These results imply that (Mg,Fe)SiO(3) liquid becomes more dense than coexisting solid at ∼1,800 km depth in the lower mantle. Soon after the Earth's formation, the heat dissipated by accretion and internal differentiation could have produced a dense melt layer up to ∼1,000 km in thickness underneath the solid mantle. We also infer that (Mg,Fe)SiO(3) perovskite is on the liquidus at deep mantle conditions, and predict that fractional crystallization of dense magma would have evolved towards an iron-rich and silicon-poor composition, consistent with seismic inferences of structures in the core-mantle boundary region.
The melting temperature of Earth's mantle provides key constraints on the thermal structures of both the mantle and the core. Through high-pressure experiments and three-dimensional x-ray microtomographic imaging, we showed that the solidus temperature of a primitive (pyrolitic) mantle is as low as 3570 ± 200 kelvin at pressures expected near the boundary between the mantle and the outer core. Because the lowermost mantle is not globally molten, this provides an upper bound of the temperature at the core-mantle boundary (T(CMB)). Such remarkably low T(CMB) implies that the post-perovskite phase is present in wide areas of the lowermost mantle. The low T(CMB) also requires that the melting temperature of the outer core is depressed largely by impurities such as hydrogen.
CD13, a receptor for human coronavirus 229E (HCoV-229E), was identified as a major component of the Triton X-100-resistant membrane microdomain in human fibroblasts. The incubation of living fibroblasts with an anti-CD13 antibody on ice gave punctate labeling that was evenly distributed on the cell surface, but raising the temperature to 37°C before fixation caused aggregation of the labeling. The aggregated labeling of CD13 colocalized with caveolin-1 in most cells. The HCoV-229E virus particle showed a binding and redistribution pattern that was similar to that caused by the anti-CD13 antibody: the virus bound to the cell evenly when incubated on ice but became colocalized with caveolin-1 at 37°C; importantly, the virus also caused sequestration of CD13 to the caveolin-1-positive area. Electron microscopy confirmed that HCoV-229E was localized near or at the orifice of caveolae after incubation at 37°C. The depletion of plasmalemmal cholesterol with methyl -cyclodextrin significantly reduced the HCoV-229E redistribution and subsequent infection. A caveolin-1 knockdown by RNA interference also reduced the HCoV-229E infection considerably. The results indicate that HCoV-229E first binds to CD13 in the Triton X-100-resistant microdomain, then clusters CD13 by cross-linking, and thereby reaches the caveolar region before entering cells.Recent studies have revealed that the plasma membranes of cells contain microdomains with discrete molecular compositions. Rafts are sphingolipid-and cholesterol-rich membrane microdomains that are thought of as platforms for signal transduction (39, 40). Although there are still many controversies regarding how rafts exist in living cells, it is generally agreed that cholesterol is indispensable for their integrity and that the detergent-resistant membrane (DRM) fraction is the in vitro correlate of the raft. Because acyl chains of sphingolipids and glycosylphosphatidylinositol (GPI)-anchored proteins enriched in the DRM fraction are more highly saturated than those of glycerolipids in the bulk membrane, the raft domain is thought to show less fluidity than nonraft areas of the plasma membrane. However, it is difficult to capture rafts morphologically because their shape and size are likely to change dynamically (40).On the other hand, caveolae were first defined morphologically as invaginations of the plasma membrane (49). They are also susceptible to cholesterol depletion (31). Moreover, caveolin-1, -2, and -3, which were identified as major components of caveolae (31,35,44,47), are highly enriched in the DRM fraction (2,12,14,36). Several results suggest that many molecules are shared by rafts and caveolae but that at least several molecules that are enriched in the DRM fraction are not concentrated in caveolae (11). Thus, caveolae are not simply a stabilized form of rafts, but there should be a regulatory mechanism (as yet unknown) to control the molecular distribution between caveolae and rafts.It has been shown that cross-linked raft molecules, such as GPI-anchored proteins,...
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