Deciphering the relationship between caveolae-mediated intracellular transport and signalling events

The caveolae-mediated transport across polarized epithelial cell barriers has been largely deciphered in the last decades and is considered the second essential intracellular transfer mechanism, after the clathrin-dependent endocytosis. The basic cell biology knowledge was supplemented recently, with the molecular mechanisms beyond caveolae generation implying the key contribution of the lipid-binding proteins (the structural protein Caveolin and the adapter protein Cavin), along with the bulb coat stabilizing molecules PACSIN-2 and Eps15 homology domain protein-2. The current attention is focused also on caveolae architecture (such as the bulb coat, the neck, the membrane funnel inside the bulb, and the associated receptors), and their specific tasks during the intracellular transport of various cargoes. Here, we resume the present understanding of the assembly, detachment, and internalization of caveolae from the plasma membrane lipid raft domains, and give an updated view on transcytosis and endocytosis, the two itineraries of cargoes transport via caveolae. The review adds novel data on the signalling molecules regulating caveolae intracellular routes and on the transport dysregulation in diseases. The therapeutic possibilities offered by exploitation of Caveolin-1 expression and caveolae trafficking, and the urgent issues to be uncovered conclude the review.