caveolaedependent

Caveolaedependent refers to cellular processes and endocytic pathways that require caveolae, small flask-shaped invaginations of the plasma membrane. Caveolae are enriched in cholesterol and sphingolipids and are organized into platforms by caveolin proteins, forming a distinctive coat with auxiliary cavin proteins. In most non-muscle cells, caveolin-1 (Cav-1) is essential, whereas caveolin-3 (Cav-3) is predominant in skeletal and cardiac muscle.

Caveolae-mediated or caveolae-dependent endocytosis is generally clathrin-independent and dynamin-dependent. It can internalize a subset of lipids, proteins, and toxins, and often traffics cargo to caveosome-like compartments, with possible routing to the endoplasmic reticulum or Golgi, instead of the canonical early endosome. Classic examples include cholera toxin B subunit and certain GPI-anchored proteins, as well as receptors that signal from cholesterol-rich domains.

Physiological roles include transcytosis across endothelial barriers, regulation of signal transduction by compartmentalizing signaling molecules (such as Src family kinases), and maintenance of lipid homeostasis. Caveolae also participate in mechanotransduction and vascular function. The precise routing of caveolae-dependent cargo can be context-dependent and influenced by cholesterol levels, cytoskeletal dynamics, and receptor engagement.

Dysfunction of caveolae or caveolin/cavin components is implicated in disease and physiology. Cav-1 or Cav-2 knockout models show disrupted caveolae formation and altered vascular permeability, while Cav-3 mutations underlie certain muscular dystrophies. Experimental approaches to study caveolae include cholesterol depletion (e.g., cyclodextrins), genetic knockdown or knockout of caveolins or cavins, and uptake assays using caveolar markers.