Abstract
Caveolae are flask-shaped invaginations of the plasma membrane found in numerous cell types and are particularly abundant in endothelial cells and adipocytes. The lipid composition of caveolae largely matches that of lipid rafts microdomains that are particularly enriched in cholesterol, sphingomyelin, glycosphingolipids, and saturated fatty acids. Unlike lipid rafts, whose existence remains quite elusive in living cells, caveolae can be clearly distinguished by electron microscope. Despite their similar composition and the sharing of some functions, lipid rafts appear more heterogeneous in terms of size and are more dynamic than caveolae. Following the discovery of caveolin-1, the first molecular marker as well as the unique scaffolding protein of caveolae, we have witnessed a remarkable increase in studies aimed at investigating the role of these organelles in cell functions and human disease. The goal of this review is to discuss the most recent studies related to the role of caveolae and caveolins in endothelial cells. We first recapitulate the major embryological processes leading to the formation of the vascular tree. We next discuss the contribution of caveolins and cavins to membrane biogenesis and cell response to extracellular stimuli. We also address how caveolae and caveolins control endothelial cell metabolism, a central mechanism involved in migration proliferation and angiogenesis. Finally, as regards the emergency caused by COVID-19, we propose to study the caveolar platform as a potential target to block virus entry into endothelial cells.
Highlights
The plasma membrane (PM) is likely the most crucial structure that safeguards and grants essential functions of eukaryotic cells
One of the well-known function of endothelial caveolae is transcytosis [13], which is the transport of macromolecules such as albumin, insulin, and LDL from the luminal side of the blood vessel to the subendothelial space—a mechanism that exhibits its greatest specialization in the blood–brain barrier of brain capillaries [14]
The authors demonstrated that neither Vascular endothelial growth factor (VEGF)-induced vascular endothelial growth factor receptor 2 (VEGFR2) phosphorylation nor VEGFR2 binding to cav-1 were affected by shear stress, indicating that caveolae may function as a platform where shear stress-sensitive receptors can safely bind their ligands while avoiding being exposed to shear stress [110]
Summary
The plasma (or cytoplasmic) membrane (PM) is likely the most crucial structure that safeguards and grants essential functions of eukaryotic cells. The preferential segregation of glycosphingolipids and cholesterol within the exoplasmic leaflet of the PM [3,4] induces the formation of “liquid-ordered” less fluid domains termed lipid rafts (LRs) that are resistant to solubilization with nonionic detergents at low temperature [5,6]. This unique biophysical characteristic is crucial to separate the detergent-soluble membrane fractions (DSMs) from the detergent-resistant membrane fractions (DRMs) enriched in cholesterol, sphingolipids, and glycophosphatidylinositol (GPI)-anchored proteins [7]. We will recapitulate here the most relevant and recent discoveries that have contributed to define the biological role of the caveolar platform in the physiopathology of the vascular endothelium
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