Sphingolipids and Membrane Domains

Sphingolipids and Membrane Domains

Sphingolipids are a group of lipids whose structure is based on sphingosine and are important in the regulation of important cell processes, e.g. apoptosis. Our studies have shown that the so-called simple sphingolipids (sphingosine, ceramide, and their 1-phosphorylated derivatives) exhibit unusual physical properties when incorporated into phospholipid bilayers. Ceramide is often formed in membranes in response to stress through the activity of sphingomyelinases, enzymes that cleave sphingomyelin into ceramides and water-soluble products. Ceramides are notorious for their low miscibility with other lipids, giving rise to lateral phase segregation and formation of ceramide-enriched domains. Sphingosine is also known for facilitating formation of gel-phase domains in membranes and its properties may explain the pathogenesis of Niemann-Pick type C disease. Recent lipidomic analysis of mammalian cells as revealed that non-canonical forms of sphingolipids, based on sphingosine analogues, are common in membranes. Our current research in this area includes unravelling the properties of a novel ternary gel phase, composed of sphingomyelin, ceramide and cholesterol, and exploring the membrane behaviour of a recently discovered family of 1-deoxyceramides, that may be related to discusses like hereditary sensory autonomic neuropathies and diabetes.

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