Revisiting the endocytic process
Most mammalian cell membranes possess small invaginations known as caveolae. These structures are implicated in many physiological processes, including vesicle trafficking, cholesterol homeostasis, signal transduction, and mechanosensing. However, the molecular mechanisms underlying caveolae function are incompletely understood, necessitating rigorous analysis. The recent identification of a new family of cavin genes prompted researchers of the EU-funded FUNCTION OF CAVEOLAE (Molecular mechanism of caveolar structure and function) project to investigate the structure and function of caveolae in vivo. Specific attention was given to the role of cavin proteins in the formation and function of caveolae. Scientists examined caveolin and cavin complexes purified from different murine tissues. They discovered that the size of these complexes varied among tissues, with lung and fat containing smaller size complexes, as compared to heart and kidney tissues. Then, using mice lacking specific cavin genes they concluded that endothelial caveolae were heterogeneous, and identified cavin 2 protein as a key molecular determinant of this heterogeneity. Previous reports had proposed a role for caveolae in intracellular trafficking, potentially by acting as autonomous vesicles. To address this, scientists fluorescently tagged caveolin-1 and cavin-1 proteins and used several imaging techniques to study the direct involvement of caveolae in endocytosis. They observed co-localisation of these proteins in caveolae dynamic structures, verifying their implication in the endocytic process, albeit at a lower fraction than initially envisaged. Further experimentation indicated that bulk plasma membrane proteins were excluded from caveolae and suggested a role in lipid trafficking. Using caveolin knockout cells, scientists observed that loss of caveolae caused mis-sorting of certain lipids to lysosomes. Collectively, the results of the study validated previous findings on the role of caveolae in endocytosis and further extended their implication in the maintenance of lipid homeostasis of the plasma membrane.
Keywords
Endocytic process, cell membrane, caveolae, cavin, caveolin, lipid homeostasis
