Membrane sphingolipids

Merrill AH, Sweeley CC Sphingolipids metabolism and cell signaling. In Biochemistry of Lipids, Lipoproteins and Membranes. Vance DE, Vance JE (editors). Elsevier, 1996. 

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. 

Haidar, K. Sphingolipid synthesis and membrane formation by Plasmodium. Tr. Cell Biol. 1996, 6, 398 05. 

Compound lipids (phospholipids, sphingolipids, glycolipids, and cholesterol and its esters) that make part of the biomembrane are subject to a less active renew-al as compared with triacylglycerides. Their renewal is associated either with the restoration of an impaired portion of the membrane, or with the replacement of a defective molecule by a new one. 

In aqueous systems, membrane lipids may exist in a gel-like solid state or as a two-dimensional liquid. In the case of pure phospholipids, these states interconvert at a well-defined transition temperature, Tc, that increases with alkyl chain length and decreases with introduction of alkyl chain unsaturation. In cell membranes, which have marked heterogeneity in both the polar and nonpolar domains of the bilayer, this state is described as liquid disordered . The presence of sufficient sphingolipids, with... 

Because membranes components participate in nearly every cell activity their structures are also dynamic and far from the equilibrium states that are most readily understood in biophysical terms. Newly synthesized bilayer lipids are initially associated with endoplasmic reticulum (Ch.3) whereas phospholipids initially insert into the cytoplasmic leaflet while cholesterol and sphingolipids insert into the luminal endoplasmic reticulum (ER) leaflet. Glycosylation of ceramides occurs as they transit the Golgi compartments, forming cerebrosides and gangliosides in the luminal leaflet. Thus, unlike model systems, the leaflets of ER membranes are asymmetric by virtue of their mode of biosynthesis. 

London, E. and Brown, D. A. (2000) Insolubility of lipids in triton X-100 physical origin, and relationship to sphingolipid/cholesterol membrane domains (rafts) Biochim. Biophys. Acta 1508,182-195. 

Despite the weakness and short-range nature of protein-lipid and lipid-lipid interactions, cells have nevertheless evolved means of laterally assembling into membrane-mi-crodomains. Sphingolipid-cholesterol rafts serve to recmit a specific set of membrane proteins and exclude others [24]. Caveolae are deeply invaginated raft domains that are stabilized by caveolin protein oligomers (binding cholesterol) [25]. 

Puri V, Watanabe R, Singh RD, et al. Clathrin-dependent and -independent internalization of plasma membrane sphingolipids initiates two Golgi targeting pathways. J Cell Biol 2001 154(3) 535-547. 

Molecular targets have been elucidated for Dm-AMPl and Rs-AFP2. Dm-AMPl was found to bind plasma membranes from Neurospora crassa and Saccharomyces cerevisiae in a saturable manner and it competed with closely related defensins for binding. Mutational studies with S. cerevisiae identified lipid raffs containing sphingolipids as a molecular target " while glycosylphosphatidylinositol (GPI)-anchored proteins could be... 

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