Research

Sphingolipid complexity and fine-tuning

Although the idea that cell membrane lipid bilayers do little more than give shape and form to cells and limit diffusion between cells and their environment is totally passé, the structural, compositional, and functional complexity of lipid bilayers often catches cell and molecular biologists by surprise. Models of lipid bilayer structure have developed considerably since the heyday of the fluid mosaic model, principally by the discovery of the restricted diffusion of membrane proteins and lipids within the plane of the bilayer. We recently suggested that further refinement of current models is necessary and proposed that describing lipid bilayers as “finely-tuned molecular assemblies” best portrays their complexity and function.

Evolution of the sphingolipid biosynthetic pathway

Sphingolipids are unique among eukaryotic cell lipids inasmuch as their biosynthesis is compartmentalized between the endoplasmic reticulum (ER) and the Golgi apparatus. This compartmentalization was first recognized about thirty years ago, and the lab is currently studying the ramifications of this feature for our understanding of how the pathway could have evolved. Studies over many decades have identified the enzymes in the pathway, their localization, topology, and an array of regulatory mechanisms.

The sphingolipid anteome

Advances in mass spectrometry have led to the realization that the number and combinatorial complexity of lipids, including sphingolipids, is much greater than previously appreciated. Sphingolipids are generated de novo by four enzymes, namely serine palmitoyltransferase, 3-ketodihydrosphingosine reductase, ceramide synthase, and dihydroceramide D4-desaturase 1.