Molecular and cellular biology of caveolae: Paradoxes and plasticities

Caveolae are 50-100 nm invaginations that represent an appendage or subcompartment of the plasma membrane. They are found in most cell types but are abundant in fibroblasts, adipocytes, endothelial cells, type I pneumocytes, epithelial cells, and smooth and striated muscle cells. Functionally, caveolae have been implicated in three major processes: endothelial transcytosis, potocytosis, and signal transduction. Caveolin, a 21-24 kD integral membrane protein, is a principal component of the caveolar membrane in vivo. Within caveolar microdomains, caveolin functions as a multivalent docking site for recruiting and sequestering signaling molecules. More specifically, caveolin interacts directly in a regulated manner with multiple lipid-modified signaling molecules (such as Src-tyrosine kinases, Gα subunits, and H-Ras), preferring the inactive conformation of these molecules. Here, we present a general overview of our current knowledge of caveolae and caveolin functioning and possible implications for treatment of human disease.