Gangliosides lipid microdomains

Simons, M., Friedrichson, T., Schulz, J.B., Pitto, M., Masserini, M., and Kurzchalia, T.V. (1999) Exogenous administration of gangliosides displaces GPI-anchored proteins from lipid microdomains in living cells. Mol. Biol. Cell 10, 3187-3196. 

Other interfacial chemistries are found in juxtamem-brane domains of certain proteins that show a preferential interaction with specific lipids in their head group region. Important lipids involved in these interactions include the polyphosphate phosphatidylinositol lipids, cholesterol, gangliosides, and sphingomyelin. Interfacial chemistries play a role in the formation of microdomains and can determine the effective concentration of certain amphiphilic drugs in different membranes or even in different leaflets of the same membrane. 

However, when the proteins fall on tiie 2D surface of the membrane, tiiis distance is significantly decreased. The effect is potentiated by tiie fact that the attachment of the amyloid protein on the membrane is not stochastic. Indeed, a common feature of amyloid proteins is that they have a marked preference for glycosphingolipids (e.g., gangliosides) that are concentrated in relatively small microdomains of tiie plasma membrane (lipid rafts). Thus, landing on a lipid raft will result in an important concentration of the amyloid protein, and this effect is potentiated by the reduction of dimensionality (Fig. 8.5). Moreover, the head groups of glycolipid clusters will exert a chaperone effect that forces the amyloid protein to adopt a secondary structure, which, depending on the protein-lipid stoichiome, can be either an a-helix or a (3-rich stmcture. ... 

The two partners are the membrane and the infectious protein (e.g., Alzheimer s -amyloid peptide Ap, Parkinson s associated a-synuclein, and HIV-1 gpl20) (Fig. 14.1A-C). Each of these proteins faces a complex membrane formed by a collection of lipids with wide biochemical diversity. Hopefully, among the myriad of brain membrane lipids, the protein generally selects a preferred target, most often located in a lipid raft microdomain. For instance, Ap peptides interact preferentially with ganglioside GMl, and a-synuclein with GM3. ... 

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