doi: 10.1161/01.RES.0000228464.97010.ee
© 2006 American Heart Association, Inc.
Editorials |
Sphingolipids and Transient Receptor Potential Channels
Evolutionarily Ancient Families Now Joined
From the Departments of Neurosurgery, Physiology, and Pathology, University of Maryland, Baltimore.
Correspondence to Dr J. Marc Simard, Department of Neurosurgery, 22 S Greene St, Suite 12SD, Baltimore, MD 21201-1595. E-mail msimard@surgery1.umaryland.edu
See related article, pages 1381–1389
Key Words: sphingosine-1-phosphate • transient receptor potential channel • transcription factor • atherosclerosis • restenosis
An extract of the first 250 words of the full text is provided, because this article has no abstract. |
Sphingolipids are one of three main classes of lipids in the cell membrane, the others being glycerolipids and sterols. Whereas sphingolipids were initially considered to act only as structural components of biological membranes, recent studies have shown that they also act as both first and second messengers in a variety of signaling pathways and have important roles in membrane microdomains called "lipid rafts."1 Like the other classes of lipids, sphingolipids exhibit an enormous combinatorial structural diversity that enables functional specialization. At present, functional roles in signal transduction pathways have been elucidated mainly for the simpler sphingolipids, ceramide, sphingosine, and spingosine-1-phospate (S1P).
The sphingolipid metabolite, S1P, is an evolutionarily ancient signaling molecule that functions in plants, yeast, and mammals. Its conserved actions across phylogenetic systems is consistent with important biological roles. In higher eukaryotes, S1P is the ligand for a family of 5 G protein–coupled receptors. These S1P receptors are differentially expressed, coupled to various G proteins, and regulate angiogenesis, vascular maturation, cardiac development, and immunity, and are important for directed cell movement.2
Similarly, the transient receptor potential (TRP) proteins, originally discovered in the fruit fly Drosophila, comprise a family of evolutionarily ancient effector molecules.3–6 TRP channels are activated by diverse non–voltage-dependent mechanisms, and appear to form many of the non–voltage-gated cationic channels found in a variety of cells. They mediate transmembrane flux of cations down their electrochemical gradients, thereby raising intracellular Na+ and Ca2+ concentrations, resulting in depolarization of the cell and activation of effector proteins sensitive to a
Related Article:
Circ. Res. 2006 98: 1381-1389.