Lipids raft signaling

GPI anchoring is a posttranslational modification occurring in the endoplasmic reticulum where preassembled GPI anchor precursors are transferred to proteins bearing a C-terminal GPI signal sequence. The GPI anchor precursors are synthesized in the endoplasmic reticulum by sequential addition of sugar and other components to phosphatidylinositol. Protein GPI anchors are ubiquitous in eukaryotic cells. In mammalian cells, GPI anchored proteins are often found in lipid rafts which are subdomains of the plasma membrane, containing various signaling components. 

Lipid rafts are specific subdomains of the plasma membrane that are enriched in cholesterol and sphin-golipids many signaling molecules are apparently concentrated in these subdomains. 

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. 

Simons K, Toomre D. Lipid rafts and signal transduction. Nat Rev 2000 1 31-39. 

Foster, L. J., de Hoog, C. L. and Mann, M. Unbiased quantitative proteomics of lipid rafts reveals high specificity for signaling factors. Proc. Natl. Acad. Sci. U.S.A. 100 5813— 5818,2003. 

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. 

Zajchowski, L.D. Robbins, S.M. (2002) Lipid rafts and little caves compartmentalized signalling in membrane microdomains. Eur. J. Biochem. 269, 737-752. 

Tsui-Pierchala, B.A., Encinas, M., Milbrandt, J., Johnson, E.M., Jr. (2002) Lipid rafts in neuronal signaling and function. Trends Neurosci. 25, 412-417. 

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. 

Fujimura Y, Tachibana H, Yamada K. 2004. Lipid raft-associated catechin suppresses the FceRI expression by inhibiting phosphorylation of the extracellular signal-regulated kinasel/2. FEBS Lett 556 204-210. 

Ceramide or N-acylsphingosine is a component of microdomains or lipid rafts. These structures serve as platforms for neural cell signaling and events related to signal transduction. Ceramide is generated either by de novo synthesis or by hydrolysis... 

Recent evidence also suggests that the distribution of phospholipids and proteins within the cell membrane is not random, but that certain areas of the cell membrane are organized into special regions or domains. 35,52 63 In particular, certain domains appear to consist primarily of lipids such as cholesterol and sphingolipids.27,50 These lipid domains are often described as lipid rafts that move freely about the cell membrane and these lipid rafts appear to be important in controlling various cell functions including cell signaling, endocytosis, and ion channel function.27,50 Future research will help further define the role of the lipid rafts and other specific domains within the cell membrane. 

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