Sphingolipids are ubiquitous in eukaryotic cells where they have been attributed a plethora of functions from the formation of structural domains to polarized cellular trafficking and signal transduction. Recent research has identified and characterised many of the key enzymes involved in sphingolipid metabolism and this has led to a heightened interest in the possibility of targeting these pro...

The formation of sphingolipid-cholesterol microdomains in cellular membranes has been proposed to function in sorting and transport of lipids and proteins as well as in signal transduction. An increasing number of cell biological and biochemical studies now supports this concept. Here we discuss the structural properties of lipids in a cell biological context. The sphingolipid-cholesterol micro...

The sphingolipids are a class of lipids that serve as integral components of eukaryotic cell membranes (21, 49). Although previously considered to be simply structural molecules, sphingolipids have more recently been shown to act as signaling molecules in many cellular functions and to play crucial roles in the regulation of pathobiological processes, such as cancer, cardiovascular and neurodeg...

Cell membranes display a tremendous complexity of lipids and proteins designed to perform the functions cells require. To coordinate these functions, the membrane is able to laterally segregate its constituents. This capability is based on dynamic liquid-liquid immiscibility and underlies the raft concept of membrane subcompartmentalization. Lipid rafts are fluctuating nanoscale assemblies of s...

ISP-1 is a new type of immunosuppressant, the structure of which is homologous to that of sphingosine. In a previous study, ISP-1 was found to inhibit mammalian serine palmitoyltransferase, the primary enzyme involved in sphingolipid biosynthesis, and to reduce the intracellular pool of sphingolipids. ISP-1 induces the apoptosis of cytotoxic T cells, which is triggered by decreases in the intra...

Methods to systematically test drugs against all possible proteins in a cell are needed to identify the targets underlying their therapeutic action and unwanted effects. Here, we show that a genome-wide drug-induced haploinsufficiency screen by using yeast can reveal drug mode of action in yeast and can be used to predict drug mode of action in human cells. We demonstrate that dihydromotuporami...

Metabolic stable isotope incorporation and secondary ion mass spectrometry (SIMS) depth profiling performed on a Cameca NanoSIMS 50 were used to image the (18)O-cholesterol and (15)N-sphingolipid distributions within a portion of a Madin-Darby canine kidney (MDCK) cell. Three-dimensional representations of the component-specific isotope distributions show clearly defined regions of (18)O-choles...

Sphingomyelin is a major sphingolipid species in animal cells and is a major lipid constituent of plasma membranes. Recent reports have established important roles for sphingomyelin and its metabolites as second messengers in signal transduction events during development and differentiation. Sphingomyelin is also a major component of sphingolipid, cholesterol-rich plasma membrane microdomains, ...

Eleven compounds were examined for their capacity to inhibit the first enzyme of the sphingolipid pathway, 3-ketodihydrosphingosine synthetase. Of these, L-cycloserine was the most potent, affecting both bacterial and brain microsomal enzymes to a significant degree at 0.04 mM. D- and L-cycloserine irreversibly inactivated the enzyme, indicating a suicide substrate mode of action. L-Cycloserine...