Sphingolipids roles

Sphingolipid Role in steroidogenesis Upstream inducers Downstream targets... 

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. 

Buccliero, R. and Futerman, H. The roles of ceramide and complex sphingolipids in neuronal cell function. Pharm. Res. 47 409-419, 2003. 

Figure 1. Scheme of sphingolipid metabolism and the central role of ceramide and ceramidases. 

Acid CDase is localized in the lysosomes and it is suggested that it plays an important role in the catabolic pathway of sphingolipids. It has been also suggested recently, to play a role in apoptosis in response to TNFa induced death ofL929 cells (Strelow etal, 2000). 

Igarashi, Y. Functional roles of sphingosine, sphingosine 1-phosphate, and methylsphingosines in regard to membrane sphingolipid signaling pathways (1997) I Biochem. (Tokyo) 122, 1080-7... 

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. 

Tvrdik, P., Westerberg, R., Silve, S., Asadi, A., Jakobsson, A., Cannon, B., Loison, G. and Jacobsson, A. (2000). Role of a new mammalian gene family in the biosynthesis of very long chain fatty acids and sphingolipids../. Cell Biol., 149, 707-718. 

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