Membrane lipids play important roles in signaling reactions. They are involved in most if not all cellular signaling cascades and in a wide variety of tissue and cell types. The purpose of this review is to highlight major pathways of signaling originating in membrane lipids. Details of lipid metabolism, and its relation to protein function, will thus advance understanding of the role of lipids in health and disease.
Major classes of lipids including glycerophospholipids, their metabolites (eicosanoids, endocannabinoids), and sphingolipids have recently generated interest in the field of signal transduction. These lipids are tightly regulated and have an impact on various physiological functions. Importantly, aberrant lipid metabolism often leads to onset of pathology, and thus the precise balance of signaling lipids and their effectors can serve as biomarkers.
Membrane lipids form precursors for second messengers and functional assembly matrices on membrane domains during cellular stimulation. Many of these modifications are rapid reactions at lipid headgroups. Metabolism of the fatty acyl portion of membrane lipids leads to the generation of a bewildering complexity of lipid mediators with extended effects in space and time.
"These lipid species are ubiquitous membrane components of eukaryotic cells, as well as being found in some prokaryotic organisms and viruses (Smith and Merrill 2002). Studies in mammals and yeast have shown that they are important structural components of membranes and also serve as bioactive molecules involved in cell signalling and regulation (Dickson et al. 2006; Fernandis and Wenk 2007; Hanada et al. 1992). The unmodified sphingolipid, ceramide, is an intermediate in complex sphingolipid biosynthesis in the Golgi apparatus. "
[Show abstract][Hide abstract] ABSTRACT: Sphingolipids are key components of eukaryotic plasma membranes that are involved in many functions, including the formation signal transduction complexes. In addition, these lipid species and their catabolites function as secondary signalling molecules in, amongst other processes, apoptosis. The biosynthetic pathway for the formation of sphingolipid is largely conserved. However, unlike mammalian cells, fungi, protozoa and plants synthesize inositol phosphorylceramide (IPC) as their primary phosphosphingolipid. This key step involves the transfer of the phosphorylinositol group from phosphatidylinositol (PI) to phytoceramide, a process catalysed by IPC synthase in plants and fungi. This enzyme activity is at least partly encoded by the AUR1 gene in the fungi, and recently the distantly related functional orthologue of this gene has been identified in the model plant Arabidopsis. Here we functionally analysed all three predicted Arabidopsis IPC synthases, confirming them as aureobasidin A resistant AUR1p orthologues. Expression profiling revealed that the genes encoding these orthologues are differentially expressed in various tissue types isolated from Arabidopsis.
"Mutants lacking the genes making up this control module could not induce the reporter in either oleic acid or glycerol. Several components of this network are also involved in controlling sphingolipid and phosphatidylinositol production, two lipid species whose roles as signal messenger molecules regulating metabolism are beginning to be revealed ( Fernandis and Wenk, 2007 ; Strahl and Thorner, 2007 ). "
[Show abstract][Hide abstract] ABSTRACT: A cell regulates the number, size, and kind of each organelle it possesses in response to its particular role in an environment or tissue. Yet we still know little about how the molecular signaling networks within each cell perform such regulation. In this issue, Saleem et al. (Saleem, R.A., B. Knoblach, F.D. Mast, J.J. Smith, J. Boyle, C.M. Dobson, R. Long-O'Donnell, R.A. Rachubinski, and J.D. Aitchison. 2008. J. Cell Biol. 181:281-292) show for the first time how groups of kinases and phosphatases are organized to control when and how a cell assembles one kind of organelle, the peroxisome.
The Journal of Cell Biology 05/2008; 181(2):185-7. DOI:10.1083/jcb.200803126 · 9.83 Impact Factor
"The derepression component of the oleate activation network (Fig. 6 A) reveals previously uncharacterized roles for signaling molecules, including the sphingolipid metabolism kinase Lcb5p and a phosphatidylinositol kinase involved in vacuolar transport, Vps34p. Sphingolipids are a class of lipids that are known to play roles in signal transmission and are important regulators of the cell cycle (for reviews, see Hannun and Obeid, 2002; Fernandis and Wenk, 2007). Phosphatidylinositols are, like sphingolipids, becoming recognized as more than structural components of lipid bilayers. "
[Show abstract][Hide abstract] ABSTRACT: Reversible phosphorylation is the most common posttranslational modification used in the regulation of cellular processes. This study of phosphatases and kinases required for peroxisome biogenesis is the first genome-wide analysis of phosphorylation events controlling organelle biogenesis. We evaluate signaling molecule deletion strains of the yeast Saccharomyces cerevisiae for presence of a green fluorescent protein chimera of peroxisomal thiolase, formation of peroxisomes, and peroxisome functionality. We find that distinct signaling networks involving glucose-mediated gene repression, derepression, oleate-mediated induction, and peroxisome formation promote stages of the biogenesis pathway. Additionally, separate classes of signaling proteins are responsible for the regulation of peroxisome number and size. These signaling networks specify the requirements of early and late events of peroxisome biogenesis. Among the numerous signaling proteins involved, Pho85p is exceptional, with functional involvements in both gene expression and peroxisome formation. Our study represents the first global study of signaling networks regulating the biogenesis of an organelle.
The Journal of Cell Biology 05/2008; 181(2):281-92. DOI:10.1083/jcb.200710009 · 9.83 Impact Factor
Data provided are for informational purposes only. Although carefully collected, accuracy cannot be guaranteed. The impact factor represents a rough estimation of the journal's impact factor and does not reflect the actual current impact factor. Publisher conditions are provided by RoMEO. Differing provisions from the publisher's actual policy or licence agreement may be applicable.