Role of caveolae in stretch-sensing: implications for mechano-electric coupling

Caveolae are small flask-like invaginations of the cell membrane, first identified in the 1950s by electron microscopy (EM). They represent a specialized form of lipid raft (an area of the cell membrane enriched in cholesterol and sphingolipids) characterized by the presence of a small protein, caveolin (cav). The lipid environment, caveolin content and morphology of caveolae are central to their diverse functional roles which include co-ordination of signal transduction, cholesterol homeostasis and endocytosis. One of caveolae’s best characterized roles is as a signalosome – a compartment that brings together components of signal transduction cascades (receptors, G proteins, kinases),thereby increasing the efficiency and fidelity of signalling. It it has become clear that mechanical stimuli can alter the morphology, lipid environment and caveolin content of caveolae. These characteristics regulate the activity of proteins in caveolae, thereby supporting the view of caveolae as a component of the cellular machinery that senses and transduces mechanical stimuli. In chapter 7, the role of caveolae in stretch-sensing and mechano-electric coupling (MEC) in the heart will be considered. The focus will be the cardiac myocyte, as this is a major site of MEC in the heart.