Cholesterol membrane domains

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. 

Recently, due to increased interest in membrane raft domains, extensive attention has been paid to the cholesterol-dependent liquid-ordered phase in the membrane (Subczynski and Kusumi 2003). The pulse EPR spin-labeling DOT method detected two coexisting phases in the DMPC/cholesterol membranes the liquid-ordered and the liquid-disordered domains above the phase-transition temperature (Subczynski et al. 2007b). However, using the same method for DMPC/lutein (zeaxanthin) membranes, only the liquid-ordered-like phase was detected above the phase-transition temperature (Widomska, Wisniewska, and Subczynski, unpublished data). No significant differences were found in the effects of lutein and zeaxanthin on the lateral organization of lipid bilayer membranes. We can conclude that lutein and zeaxanthin—macular xanthophylls that parallel cholesterol in its function as a regulator of both membrane fluidity and hydrophobicity—cannot parallel the ability of cholesterol to induce liquid-ordered-disordered phase separation. 

Roy S, Luetterforst R, Harding A, et al. Dominant-negative caveolin inhibits H-Ras function by disrupting cholesterol-rich plasma membrane domains. Nat Cell Biol 1999 1(2) 98-105. 

Bastiaanse EM, Jongsma H, van der Laarse A, Takens-Kwak BR Heptanol-induced decrease in cardiac gap jnctional conductance is mediated by a decrease in the fluidity of membranous cholesterol-rich domains. J Membr Biol 1993 136 135-145. 

The second regulatory mechanism involves the degra-dation of HMG-CoA reductase. As stated in chapter 29 the amount of an enzyme in a cell is determined by both its rate of synthesis and its rate of degradation. The rate of degradation of the reductase appears to be modulated by the supply of cholesterol. Thus, when cholesterol is abundant, the rate of enzyme degradation is twice as fast as when there is a limited supply of cholesterol. The effect of cholesterol on enzyme degradation is mediated by the membrane domain of the enzyme. 

Schrattenholz A. and Soskic V. (2006). NMDA receptors are not alone dynamic regulation of NMDA receptor structure and function by neuregulins and transient cholesterol-rich membrane domains leads to disease-specific nuances of glutamate signalling. Curr. Top. Medicinal Chem. 6 663-686. 

C. Yuan, J. Furlong, P. Burgos and L. J. Johnston, The size of lipid rafts an atomic force microscopy study of ganglioside GM1 domains in sphingomyelin/ DOPC/cholesterol membranes, Biophys. J., 82 (2002) 2526-2535. 

Zeuschner, D., Stoorvogel, W. and Gerke, V. (2001) Association of annexin 2 with recycling endosomes requires either calcium- or cholesterol-stabilized membrane domains. Eur. J. Cell Biol. 80, 499-507. 

A few proteins exist that sequester PIP2 in a cholesterol-dependent manner. One of these proteins is the N-terminal myristoylated peptide of NAP-22 (33, 34). Combined confocal microscopy and AFM show that this peptide forms new cholesterol-rich domains within the liquid-disordered domain to which it attracts PIP2 (31). In addition, a peptide segment of caveolin promotes the formation of membrane domains containing both cholesterol and PIP2 (35). 

Cholesterol-rich domains of biological membranes have been isolated on the basis of their insolubility in 1% Triton at 4° C (36). This method has come into question because of the possibility that the Triton itself causes rearrangement of membrane components (37, 38). As indicated above, this fraction should not be referred to as a raft. However, the cholesterol-rich domain in the form of caveolae can be isolated without use of detergent (39, 40), providing stronger evidence that this cholesterol-rich domain exists in a biological membrane before extraction. 

Epand RM, Vuong P, Yip CM, Maekawa S, Epand RE. Cholesterol-dependent partitioning of Ptdlns(4,5)P-2 into membrane domains by the N-terminal fragment of NAP-22 (neuronal axonal myristoylated membrane protein of 22kDa). Biochem. J. 2004 379 527-532. 

In 1997, Simons and Ikonen (8) proposed that strongly ordered membrane domains rich in cholesterol and sphingolipids would be involved in a variety of cellular processes such as signal... 

Lipid rafts A membrane domain that is enriched in cholesterol. 

In recent years, much evidence has accumulated for lateral membrane domains that differ in their relative cholesterol content (Schroeder et al., 1995), In addition, it has been proposed that high levels of sn-2 unsaturation may promote formation of microdomains, in which the saturated sn-1 chains preferentially interact with each other (Litman et al., 1991). Several studies ofcholesterol in bilayers containing high levels of polyunsaturation have reported evidence of lateral domains, which are driven by the preference of cholesterol for saturated acyl chains over polyunsaturated acyl chains (Huster et al., 1998 Mitchell Litman, 1998b Polozova Litman, 2000 Zerouga et al, 1995), The recent... 

Schroeder RJ, Ahmed SN, Zhu Y, London E, Brown DA. Cholesterol and sphingolipid enhance the Triton X-100 insolubility of glycosylphosphatidylinositol-anchored proteins by promoting the formation of detergent-insoluble ordered membrane domains. J Biol Chem 1998 273 1150-1157. 

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