Caveolaemediated

Caveolae-mediated endocytosis is a clathrin-independent cellular uptake pathway that uses caveolae, small flask-shaped invaginations of the plasma membrane, as entry points for selective cargo. These membrane domains are enriched in cholesterol, sphingolipids, and the scaffolding proteins caveolin-1 and caveolin-2, with cavin family proteins helping stabilize the structure. Caveolae are dynamic platforms that can participate in endocytosis, transcytosis, and signal regulation.

Caveolins form the structural scaffold of caveolae, with caveolin-1 being the most widely expressed in many cell types, caveolin-2 often co-expressed, and caveolin-3 specialized to muscle. Cavins, particularly cavin-1 (PTRF), are essential for caveolae formation and stability. Endocytic budding and vesicle scission in caveolae commonly involve dynamin and may lead to delivery of cargo to endosomes or direct transcytosis across polarized cells, such as endothelial cells.

Cargo associated with caveolae-mediated uptake includes certain lipids, cholesterol esters, albumin, and a subset of pathogens or toxins, exemplified by cholera toxin B in some cell types and simian virus 40 in permissive cells. In endothelial cells, caveolae also participate in transcytosis, helping transport molecules across the vascular barrier. In addition to trafficking, caveolae function as signaling hubs; caveolin-1 binds and modulates signaling proteins such as endothelial nitric oxide synthase and Src family kinases, influencing pathways related to vascular tone and metabolism.

Dysregulation of caveolae or caveolin proteins has been linked to metabolic disorders, muscular diseases, and altered pathogen susceptibility. The pathway remains a distinct and versatile component of cellular membrane dynamics, complementing clathrin-mediated endocytosis and other uptake routes.