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Líneas de Investigación

Caveolins in the endoplasmic reticulum: homeostatic cholesterol sensors?

Resumen

Caveolins (CAVs) are essential components of caveolae; plasma membrane invaginations with reduced fluidity, reflecting cholesterol accumulation. CAV proteins bind cholesterol, and CAV’s ability to move between cellular compartments helps control intracellular cholesterol fluxes.

Descripción

CAVs are essential components of caveolae; plasma membrane invaginations with reduced fluidity, reflecting cholesterol accumulation. CAV proteins bind cholesterol, and CAV’s ability to move between cellular compartments helps control intracellular cholesterol fluxes. In humans, CAV1 mutations result in lipodystrophy, cell transformation, and cancer. CAV1 gene-disrupted mice exhibit cardiovascular diseases, diabetes, cancer, atherosclerosis, and pulmonary fibrosis. The mechanism(s) underlying these disparate effects are unknown.

 

In 1999 we described for the first time the presence of CAVs in endosomes (Pol et al., Hepatology 1999) and our work was pioneering in the study of endosomes as signaling platforms (Pol et al., FEBS lett 1998). Our current model suggests that CAV is a cholesterol transporter and proposes an alternative view of caveolae. It has been suggested that mammalian cells use caveolae and LDs to ensure a supply of lipid-raft components to the cell when needed and indeed, regulatory circuits that coordinate their functions are followed by CAV (Pol et al., J Cell Biol 2001; Pol et al., Mol Biol Cell 2004).

 

However, since cholesterol levels in different sub-cellular membranes can change the organelles function (as we demonstrated for mitochondria, see below), it is likely important to have ‘storehouse’ locations where it is possible to rapidly sequester as well as release extra cholesterol until needed, but where such changes will not impair cellular function. We hypothesize that caveolae may serve this role. We are now working on this hypothesis, studying the intracellular cholesterol imbalance caused by the lack of function of caveolin and the consequences on the cell metabolism, proliferation and survival.

Caveolin and cholesterol trafficking
Caveolin and cholesterol trafficking
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