Caveolae signaling

Fyn is a nonreceptor tyrosine kinase related to Src that is frequently found in cell junctions. Die protein is N-myristoylated and palmitoylated and thereby becomes associated with caveolae-like membrane microdomains. Fyn can interact with a variety of other signaling molecules and control a diversity of biological processes such as T cell receptor signaling, regulation of brain function, and adhesion mediated signaling. 

While the fluid mosaic model of membrane stmcture has stood up well to detailed scrutiny, additional features of membrane structure and function are constantly emerging. Two structures of particular current interest, located in surface membranes, are tipid rafts and caveolae. The former are dynamic areas of the exo-plasmic leaflet of the lipid bilayer enriched in cholesterol and sphingolipids they are involved in signal transduction and possibly other processes. Caveolae may derive from lipid rafts. Many if not all of them contain the protein caveolin-1, which may be involved in their formation from rafts. Caveolae are observable by electron microscopy as flask-shaped indentations of the cell membrane. Proteins detected in caveolae include various components of the signal-transduction system (eg, the insutin receptor and some G proteins), the folate receptor, and endothetial nitric oxide synthase (eNOS). Caveolae and lipid rafts are active areas of research, and ideas concerning them and their possible roles in various diseases are rapidly evolving. 

Liu, L., Mohammadi, K., Aynafshar, B. et al. Role of caveolae in the signal transducing function of cardiac Na+/K+-ATPase. Am. J. Physiol. Cell Physiol. 284 C1550-C1560, 2003. 

A. A. Wolf, M. G. Jobling, S. Wimer-Mackin, M. Ferguson-Maltzman, J. L. Madara, R. K. Holmes, and W. I. Lencer. Ganglioside structure dictates signal transduction by cholera toxin and association with caveolae-like membrane domains in polarized epithelia. J Cell Biol. 141 917-927 (1998). 

Liu, J., Oh, P., Horner, T., Rogers, R. A., and Schnitzer, J. E., 1997, Organized endothelial cell surface signal transduction in caveolae distinct fromglycosylphosphatidyhnositol-anchored protein microdomains./. Biol. Chem. 272 7211-7222. 

Cholesterol is an important structural component of cellular membranes, where it plays a role in modulating membrane fluidity and phase transitions, and, together with sphingomyelin, forms lipid rafts or caveolae, which are sites where proteins involved in diverse signaling pathways become concentrated. Furthermore, cholesterol is a precursor of oxysterols, steroid hormones, and bile acids. 

Caveolin is an integral membrane protein that associates with the inner leaflet of the plasma membrane, forcing it to curve inward to form caveolae, probably involved in membrane transport and signaling. 

Membrane Rafts and Caveolae May Segregate Signaling Proteins... 

Membrane rafts and caveolae sequester groups of signaling proteins in small regions of the plasma membrane, enhancing their interactions and making signaling more efficient. 

Now covers the roles of membrane rafts and caveolae in signaling pathways, including the activities of AKAPs (A Kinase Anchoring Proteins) and other scaffold proteins... 

Other vesicles are surrounded by nonclathrin membrane coats. Some of these originate from caveolae (little caves), which act in endocytosis, exocytosis, and transmembrane signaling.564abc A coatomer complex of eight subunits with molecular masses from 20 to 60 kDa coats vesicles involved in transport between compartments of the Golgi.565-567... 

Targeting of proteins to specialized domains of a membrane are less well understood. These include caveolae and lipid rafts, domains that are high in cholesterol and sphingolipids and which function in endocytosis and in cell signaling. A recent proposal is that proteins with hydrophobic surfaces needed in these domains become coated with a lipid "shell" before entering the membrane.6173... 

Insel, P. A., Head, B. P., Patel, H. H., Roth, D. M., Bundey, R. A., and Swaney, J. S. (2005b). Compartmentation of G-protein-coupled receptors and their signalling components in lipid rafts and caveolae. Biochem. Soc. Trans. 33, 1131-1134. 

Ostrom, R. S., and Insel, P. A. (2004). The evolving role of lipid rafts and caveolae in G protein-coupled receptor signaling Implications for molecular pharmacology. 

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