▪ Abstract Lysophospholipids (LPs), such as lysophosphatidic acid and sphingosine 1-phosphate, are membrane-derived bioactive lipid mediators. LPs can affect fundamental cellular functions, which include proliferation, differentiation, survival, migration, adhesion, invasion, and morphogenesis. These functions influence many biological processes that include neurogenesis, angiogenesis, wound healing, immunity, and carcinogenesis. In recent years, identification of multiple cognate G protein-coupled receptors has provided a mechanistic framework for understanding how LPs play such diverse roles. Generation of LP receptor-null animals has allowed rigorous examination of receptor-mediated physiological functions in vivo and has identified new functions for LP receptor signaling. Efforts to develop LP receptor subtype-specific agonists/antagonists are in progress and raise expectations for a growing collection of chemical tools and potential therapeutic compounds. The rapidly expanding literature on the LP re...

http://www.scripps.edu/chun/PDFs/Ishii%20Ann%20Rev%20Biochem%202004.pdf

Lysophospholipid receptors: Signaling and biology

The yeast Saccharomyces cerevisiae is a powerful experimental system to study biochemical, cell biological and molecular biological aspects of lipid synthesis. Most but not all genes encoding enzymes involved in fatty acid, phospholipid, sterol or sphingolipid biosynthesis of this unicellular eukaryote have been cloned, and many gene products have been functionally characterized. Less information is available about genes and gene products governing the transport of lipids between organelles and within membranes, turnover and degradation of complex lipids, regulation of lipid biosynthesis, and linkage of lipid metabolism to other cellular processes. Here we summarize current knowledge about lipid biosynthetic pathways in S. cerevisiae and describe the characteristic features of the gene products involved. We focus on recent discoveries in these fields and address questions on the regulation of lipid synthesis, subcellular localization of lipid biosynthetic steps, cross-talk between organelles during lipid synthesis and subcellular distribution of lipids. Finally, we discuss distinct functions of certain key lipids and their possible roles in cellular processes.

Biochemistry, Cell Biology and Molecular Biology of Lipids of Saccharomyces cerevisiae

Phospholipids are emerging as novel second messengers in plant cells. They are rapidly formed in response to a variety of stimuli via the activation of lipid kinases or phospholipases. These lipid signals can activate enzymes or recruit proteins to membranes via distinct lipid-binding domains, where the local increase in concentration promotes interactions and downstream signaling. Here, the latest developments in phospholipid-based signaling are discussed, including the lipid kinases and phospholipases that are activated, the signals they produce, the domains that bind them, the downstream targets that contain them and the processes they control.

Phospholipid-based signaling in plants

The Saccharomyces cerevisiae Lipin Homolog Is a Mg2+-dependent Phosphatidate Phosphatase Enzyme

Due to its genetic tractability and increasing wealth of accessible data, the yeast Saccharomyces cerevisiae is a model system of choice for the study of the genetics, biochemistry, and cell biology of eukaryotic lipid metabolism. Glycerolipids (e.g., phospholipids and triacylglycerol) and their precursors are synthesized and metabolized by enzymes associated with the cytosol and membranous organelles, including endoplasmic reticulum, mitochondria, and lipid droplets. Genetic and biochemical analyses have revealed that glycerolipids play important roles in cell signaling, membrane trafficking, and anchoring of membrane proteins in addition to membrane structure. The expression of glycerolipid enzymes is controlled by a variety of conditions including growth stage and nutrient availability. Much of this regulation occurs at the transcriptional level and involves the Ino2–Ino4 activation complex and the Opi1 repressor, which interacts with Ino2 to attenuate transcriptional activation of UASINO-containing glycerolipid biosynthetic genes. Cellular levels of phosphatidic acid, precursor to all membrane phospholipids and the storage lipid triacylglycerol, regulates transcription of UASINO-containing genes by tethering Opi1 to the nuclear/endoplasmic reticulum membrane and controlling its translocation into the nucleus, a mechanism largely controlled by inositol availability. The transcriptional activator Zap1 controls the expression of some phospholipid synthesis genes in response to zinc availability. Regulatory mechanisms also include control of catalytic activity of glycerolipid enzymes by water-soluble precursors, products and lipids, and covalent modification of phosphorylation, while in vivo function of some enzymes is governed by their subcellular location. Genome-wide genetic analysis indicates coordinate regulation between glycerolipid metabolism and a broad spectrum of metabolic pathways.

https://www.genetics.org/content/genetics/190/2/317.full.pdf

Metabolism and Regulation of Glycerolipids in the Yeast Saccharomyces cerevisiae

https://digitalcommons.uri.edu/cgi/viewcontent.cgi?article=1002&context=chs_past_depts_facpubs

Isolation and characterization of the Saccharomyces cerevisiae DPP1 gene encoding diacylglycerol pyrophosphate phosphatase.

Mammalian Mg2+-independent Phosphatidate Phosphatase (PAP2) Displays Diacylglycerol Pyrophosphate Phosphatase Activity

Regulation of the Saccharomyces cerevisiae DPP1-encoded Diacylglycerol Pyrophosphate Phosphatase by Zinc

Regulation of the DPP1-encoded Diacylglycerol Pyrophosphate (DGPP) Phosphatase by Inositol and Growth Phase INHIBITION OF DGPP PHOSPHATASE ACTIVITY BY CDP-DIACYLGLYCEROL AND ACTIVATION OF PHOSPHATIDYLSERINE SYNTHASE ACTIVITY BY DGPP*

Xiaoming Chen

Papers

Isolation and characterization of the Saccharomyces cerevisiae DPP1 gene encoding diacylglycerol pyrophosphate phosphatase.

Mammalian Mg2+-independent Phosphatidate Phosphatase (PAP2) Displays Diacylglycerol Pyrophosphate Phosphatase Activity

Regulation of the Saccharomyces cerevisiae DPP1-encoded Diacylglycerol Pyrophosphate Phosphatase by Zinc

Regulation of the DPP1-encoded Diacylglycerol Pyrophosphate (DGPP) Phosphatase by Inositol and Growth Phase INHIBITION OF DGPP PHOSPHATASE ACTIVITY BY CDP-DIACYLGLYCEROL AND ACTIVATION OF PHOSPHATIDYLSERINE SYNTHASE ACTIVITY BY DGPP*