Lipid sensing and lipid sensors

Lipid droplets have been considered for a long time as inert intracytoplasmic deposits formed within cells under various conditions. Recently, new tools and new approaches have been used to visualize and study these intracellular structures. This revealed new aspects of lipid droplets biology and pointed out their organized structure and dynamic composition. In adipocytes, the specialized cell type for the storage of energy as fat, lipid droplets are particularly well-developed organelles and exhibit unique properties. Also discussed in this paper is the view that lipid droplets, through specific candidate constituents, can play a role in sensing the level of their lipid stores by adipocytes.     

Lipid sensing and lipid sensors

Specialized lipid microdomains in the cell plasma membrane, referred to as 'lipid rafts', are enriched in sphingolipids and cholesterol and have drawn considerable interest as platforms for the recruitment of signaling molecules. Despite numerous biochemical and cellular studies, debate persists on the size, lifetime and even the existence of lipid rafts, emphasizing the need for reliable lipid probes to study in situ membrane lipid organization. In this review, we summarize our recent data on living cells using two specific probes of raft components: lysenin, a sphingomyelin- binding protein and the fluorescein ester of poly(ethyleneglycol)cholesteryl ether that labels cholesterol-rich domains. Sphingomyelin-rich domains that are spatially and functionally distinct from the GM1 ganglioside-rich domains were found at the plasma membrane of Jurkat T cells. In addition, the dynamics of cholesterol-rich domains could be monitored at the cell surface as well as inside the cells.     

Lipid sensing and lipid sensors

The field of bile acids has witnessed an impulse in the last two decades. This has been the result of cloning the genes encoding enzymes of bile acid synthesis and their transporters. There is no doubt that the identification of Farnesoid X Receptor (FXR, NR1H4) as the bile acid receptor has contributed substantially to attract the interest of scientists in this area. When FXR was cloned by Forman et al. [1], farnesol metabolites were initially considered the physiological ligands. After identifying FXR and other nuclear receptors as bile acid sensors [2-4], it has become clear that bile acids are involved in the regulation of lipid and glucose metabolism and that these molecules are eclectic regulators of diverse cellular functions. In this review, we will summarize the current knowledge of the functions regulated by bile acids and how their physiological receptors mediate the signaling underlying numerous cellular responses.     

Lipid flippases and their biological functions

The typically distinct phospholipid composition of the two leaflets of a membrane bilayer is generated and maintained by bi-directional transport (flip-flop) of lipids between the leaflets. Specific membrane proteins, termed lipid flippases, play an essential role in this transport process. Energy-independent flippases allow common phospholipids to equilibrate rapidly between the two monolayers and also play a role in the biosynthesis of a variety of glycoconjugates such as glycosphingolipids, N-glycoproteins, and glycosylphosphatidylinositol (GPI)-anchored proteins. ATP-dependent flippases, including members of a conserved subfamily of P-type ATPases and ATP-binding cassette transporters, mediate the net transfer of specific phospholipids to one leaflet of a membrane and are involved in the creation and maintenance of transbilayer lipid asymmetry of membranes such as the plasma membrane of eukaryotes. Energy-dependent flippases also play a role in the biosynthesis of glycoconjugates such as bacterial lipopolysaccharide. This review summarizes recent progress on the identification and characterization of the various flippases and the demonstration of their biological functions. Received 12 April 2006; received after revision 22 June 2006; accepted 30 August 2006     

Lipopolysaccharide-binding molecules: transporters, blockers and sensors

Lipopolysaccharide (LPS), a major component of the outer membrane of Gram-negative bacteria, can be beneficial to the host by activating the innate immune system, or harmful, by inducing inflammation, disseminated intravascular coagulation, multiple organ failure, shock and often death. On the bacteria, and in host biological fluids and cells, LPS is never free but constantly attached to cognate-binding proteins. Understanding how LPS is transported and further recognized by sensors able to deliver a signal, or by inactivating molecules able to neutralize its biological effects, is an important goal. This review describes the large panel of peptides and proteins reported to associate with LPS, and provides information on their origin, their structure and the location of amino acid residues involved in their interaction with LPS. A better understanding of the mode of recognition of LPS by cognate proteins prompted many laboratories to design on a rational basis synthetic molecules which can be used to detect low amounts of endotoxin, or to act as efficient blockers of in vitro and in vivo responses to LPS.Received 15 January 2004; received after revision 20 February 2004; accepted 25 February 2004     

Lipid transport in microorganisms

Summary Microorganisms are useful model systems for the study of intracellular transport of lipids. Eukaryotic microorganisms, such as the yeastSaccharomyces cerevisiae, are similar to higher eukaryotes with respect to organelle structure and membrane assembly. Experiments in vivo showed that transport of phosphatidylcholine between yeast microsomes and mitochondria is energy independent; transfer of phosphatidylinositol to the plasma membrane and the flux of secretory vesicles take place by different mechanisms. Linkage of transfer and biosynthesis of phospholipids was demonstrated in the case of intramitochondrial phospholipid transfer. A yeast phosphatidylinositol/phosphatidylcholine transfer protein, which is essential for cell viability, was isolated and characterized. Another phospholipid transfer protein present in yeast cytosol, which has a different specificity, is currently under investigation. Transfer of phospholipids between cellular membranes was also demonstrated with prokaryotes. The cytoplasm and the periplasma of the gram-negative facultative photosynthetic bacteriumRhodopseudomonas sphaeroides contain phospholipid transfer proteins; these seem to be involved in the biosynthesis of prokaryotic membranes.     

Lipid composition ofMicrosporum gypseum

Summary The lipid composition ofMicrosporum gypseum has been studied. The lipids amounted to 10.1% and phospholipids to 1.1% of the mycelial dry weight. Phosphatidyl choline, phosphatidyl serine and phosphatidyl ethanolamine were the major components, while lysophosphatidyl choline, and phosphatidyl inositol were present in smaller quantities. Neutral lipids consisted of monoglycerides, diglycerides, triglycerides, free and esterified cholesterol.Acknowledgments: Thanks are due to Prof. P. Talwar, Department of Microbiology of this Institute for the supply ofM. gypseum. Technical assistance of Mr Adarsh Kumar is acknowledged.     

Lipid transfer in plants

Summary Plant cells contain cytosolic proteins, called lipid transfer proteins (LTP), which are able to facilitate in vitro intermembrane transfer of phospholipids. Proteins of this kind from three plants, purified to homogeneity, have several properties in common: molecular mass around 9 kDa, high isoelectric point, lack of specificity for phospholipids, and binding ability for fatty acids. The comparison of their amino acid sequences revealed striking homologies and conserved domains which are probably involved in their function as LTPs. These proteins could play a major role in membrane biogenesis by conveying phospholipids from their site of biosynthesis to membranes unable to form these lipids. Immunochemical methods were used to establish an in vivo correlation between membrane biogenesis and the level of LTP or the amount of LTP synthesized in vitro from mRNAs. The recent isolation of a full-length cDNA allows novel approaches to studying the participation of LTPs in the biogenesis of plant cell membranes.     

Lipid polarity and sorting in epithelial cells

Lipid polarity and sorting in epithelial cells     

Lipid mobility and function in biological membranes

Zusammenfassung Es wird vorgeschlagen, dass die Reaktion des Thiol/Disulpid Austausches zwischen Antigen oder Polypeptid-Hormon und dem Mambran-Antikörper oder Hormon-Rezeptor Iin Lymphozyten oder Plasma Membranen), der im beweglichen Membran-Lipoid suspendiert ist, einen vergrösserten Oberflächen-Komplex bildet, der das Lipid komprimiert und dadurch ein Enzym in eine kritische Konformation zusammendrückt, welch letztere die Immun-Reaktion oder c-AMP-Bildung auslöst.     

Macro domains as metabolite sensors on chromatin

How metabolism and epigenetics are molecularly linked and regulate each other is poorly understood. In this review, we will discuss the role of direct metabolite-binding to chromatin components and modifiers as a possible regulatory mechanism. We will focus on globular macro domains, which are evolutionarily highly conserved protein folds that can recognize NAD⁺-derived metabolites. Macro domains are found in histone variants, histone modifiers, and a chromatin remodeler among other proteins. Here we summarize the macro domain-containing chromatin proteins and the enzymes that generate relevant metabolites. Focusing on the histone variant macroH2A, we further discuss possible implications of metabolite binding for chromatin function.     

Lipid peroxidation in rabbit reticulocytes

Summary Lipid peroxides in rabbit erythrocytes and plasma were determined while anemia was induced by daily bleeding. They increased as reticulocytes increased and returned to normal with the morphological transformation to mature cells.This work was supported in part by a grant-in-aid from the Japan Medical Research Foundation and a grant-in-aid (project No. 56570363) from the Ministry of Education, Science and Culture of Japan.     

Lipid interactions with transmembrane proteins

Magnetic resonance results, principally from ²H-nuclear magnetic resonance, indicate that the mean lipid-chain ordering at the surface of transmembrane proteins is comparable to that in fluid lipid bilayers. Principally, it is the requirement for matching the hydrophobic lengths of lipid and protein that modulates the degree of chain ordering at the lipid-protein interface. The distribution of chain order parameters is, nonetheless, broader in the presence of integral proteins than in fluid lipid bilayers. The chain configurations of the phospholipids that are resolved in crystals of integral membrane proteins display considerable conformational heterogeneity. Chain C–C dihedral angles are, however, not restricted to the energetically allowable trans and gauche rotamers. This indicates that the chains of a given lipid do not have a unique configuration in protein crystals.     

Lipid peroxidation in rabbit reticulocytes

Lipid peroxides in rabbit erythrocytes and plasma were determined while anemia was induced by daily bleeding. They increased as reticulocytes increased and returned to normal with the morphological transformation to mature cells.     

Purines and cortisone in lipid mobilization

Zusammenfassung Purin-Basen, Kaffein und Cortison führen zu einer Vermehrung der Fettsäuren im Rattenserum. Adenin vermindert im Gegensatz zu den anderen Purinen die Lipolyse.