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BBA - Biomembranes (v.1798, #1)
Connexin-based signaling in acute myelogenous leukemia (AML) by Brynjar Foss; Karl Johan Tronstad; Øystein Bruserud (pp. 1-8).
Normal and malignant hematopoiesis are regulated by intercellular communication in the hematopoietic microenvironments, and both soluble mediators as well as direct cell–cell contact play important functional roles. Gap junctions are complex membrane structures that transfer molecules between neighboring cells and thereby alter intracellular signaling and metabolism. The gap junction building blocks, the connexins, are also involved in gap junction-independent intercellular communication by forming hemichannels that transfer substances between the intra- and extracellular spaces. Connexins are furthermore involved in cell regulation as single molecules by modulating intracellular pathways and possibly gene transcription. The role of connexins in leukemogenesis and leukemic cell functions are not well characterized. In this review, we describe the known effects of gap junctions and connexins in acute myelogenous leukemia and the diverse potential of connexins in acute myelogenous leukemia chemosensitivity, intracellular signaling and cell death regulation.
Keywords: AML; Gap junction; Hemichannel; Connexin; Chemosensitivity; Apoptosis
Adenosine receptors interacting proteins (ARIPs): Behind the biology of adenosine signaling by Francisco Ciruela; Catarina Albergaria; Aroa Soriano; Laura Cuffí; Lourdes Carbonell; Silvia Sánchez; Jorge Gandía; Víctor Fernández-Dueñas (pp. 9-20).
Adenosine is a well known neuromodulator in the central nervous system. As a consequence, adenosine can be beneficial in certain disorders and adenosine receptors will be potential targets for therapy in a variety of diseases. Adenosine receptors are G protein-coupled receptors, and are also expressed in a large variety of cells and tissues. Using these receptors as a paradigm of G protein-coupled receptors, the present review focus on how protein–protein interactions might contribute to neurotransmitter/neuromodulator regulation, based on the fact that accessory proteins impinge on the receptor/G protein interaction and therefore modulate receptor functioning. Besides affecting receptor signaling, these accessory components also play a key role in receptor trafficking, internalization and desensitization, as it will be reviewed here. In conclusion, the finding of an increasing number of adenosine receptors interacting proteins, and specially the molecular and functional integration of these accessory proteins into receptorsomes, will open new perspectives in the understanding of particular disorders where these receptors have been proved to be involved.
Keywords: G protein-coupled receptor; Adenosine receptor; Protein–protein interaction; Accessory protein; Receptor anchoring; Plasma membrane expression
The influence of different membrane components on the electrical stability of bilayer lipid membranes by Iris van Uitert; Séverine Le Gac; Albert van den Berg (pp. 21-31).
A good understanding of cell membrane properties is crucial for better controlled and reproducible experiments, particularly for cell electroporation where the mechanism of pore formation is not fully elucidated. In this article we study the influence on that process of several constituents found in natural membranes using bilayer lipid membranes. This is achieved by measuring the electroporation threshold ( Vth) defined as the potential at which pores appear in the membrane. We start from highly stable 1,2-diphytanoyl- sn-glycero-3-phosphocholine (DPhPC) membranes ( Vth ∼200 mV), and subsequently add therein other phospholipids, cholesterol and a channel protein. While the phospholipid composition has a slight effect (100 mV≤ Vth≤290 mV), cholesterol gives a concentration-dependent effect: a slight stabilization until 5% weight ( Vth ∼250 mV) followed by a noticeable destabilization ( Vth ∼100 mV at 20%). Interestingly, the presence of a model protein, α-hemolysin, dramatically disfavours membrane poration and Vth shows a 4-fold increase (∼800 mV) from a protein density in the membrane of 24×10−3 proteins/μm2. In general, we find that pore formation is affected by the molecular organization (packing and ordering) in the membrane and by its thickness. We correlate the resulting changes in molecular interactions to theories on pore formation.
Keywords: Abbreviations; DPhPC; 1,2-Diphytanoyl-; sn; -glycero-3-phosphocholine; PS; Porcine brain l-α-phosphatidylserine; PI; Bovine liver l-α-phosphatidylinositol; PE; Bovine heart l-α-phosphatidylethanolamine; PC; Phosphatidylcholine; Ch; Cholesterol; BLM; Bilayer lipid membrane; V; th; Electroporation threshold voltageElectroporation; BLM; Cell membrane; Pore formation; (Phospho)lipid; Channel protein
Influence of K+-dependent membrane lipid composition on the expression of the kdpFABC operon in Escherichia coli by Maren Schniederberend; Petra Zimmann; Mikhail Bogdanov; William Dowhan; Karlheinz Altendorf (pp. 32-39).
The membrane-bound sensor kinase KdpD and the cytoplasmic response regulator KdpE regulate the expression of the kdpFABC operon coding for the high affinity potassium uptake system KdpFABC in Escherichia coli. The signal transduction cascade of this two component system is activated under K+-limiting conditions in the medium, but is less sensitive to high osmolality. In order to test whether K+ limitation affects membrane phospholipid composition and whether this change affects kdpFABC expression, we analysed the phospholipid composition of E. coli under these conditions. Our measurements revealed that there is an increase in the cardiolipin (CL) content during the exponential growth phase at the expense of the zwitterionic phospholipid phosphatidylethanolamine. The higher anionic phospholipid content occurs along with an increase of transcriptional activity of the cls gene coding for CL synthase. Furthermore, in vivo studies with E. coli derivatives carrying mutations in genes coding for enzymes involved in phospholipid biosynthesis revealed that the increase in the anionic lipid composition enhances the expression rate of the kdpFABC operon. Finally, we show that kinase activity of KdpD is stimulated in its native membrane environment by fusion with liposomes of anionic, but reduced with liposomes of zwitterionic phospholipids.
Keywords: Abbreviations; CL; cardiolipin; PC; phosphatidylcholine; PE; phosphatidylethanolamine; PG; phosphatidylglycerol E. coli; membrane; Potassium; KdpD sensor kinase; Signal transduction; Phospholipid; Cardiolipin
Structural and thermodynamic determinants of chain-melting transition temperatures for phospholipid and glycolipids membranes by Derek Marsh (pp. 40-51).
For optimum function, biological membranes need a fluid environment, which is afforded by the liquid-disordered phase of lipids with low chain-melting temperatures or the liquid-ordered phase that is formed by combining high chain-melting lipids with cholesterol. The dependence of chain-melting transition temperature on lipid chain structure is therefore of central importance. The currently available database, including sphingolipids and glycolipids, is summarised here by parameterising systematic dependences on molecular structure in terms of suitable thermodynamic models. Chain-length dependence, chain asymmetry of lipids forming partially interdigitated and mixed interdigitated gel phases, chain unsaturation, positional dependence of methyl branching, headgroup-attached and α-branched chains, and length of zwitterionic headgroups are all covered. This type of information is essential for biophysical approaches to functional lipidomics.
Keywords: Lipid bilayer; Chain melting; Chain asymmetry; Chain unsaturation; Chain interdigitation; Branched chain; Headgroup length
A peptide based on the pore-forming domain of pro-apoptotic poliovirus 2B viroporin targets mitochondria by Vanesa Madan; Silvia Sánchez-Martínez; Luis Carrasco; José L. Nieva (pp. 52-58).
Non-structural poliovirus 2B protein induces plasma membrane permeabilization and has been recently implicated in triggering apoptosis via the mitochondrial pathway. Here we describe that the pore-forming P3 peptide, based on the 2B amphipathic domain, translocates through the plasma membrane of culture cells and targets mitochondria. Cell permeabilization by P3 versions of different lengths, together with peptide uptake analyses supported an internalization mechanism dependent on P3 capacity to interact physically with lipid bilayers and establish permeating pores therein. Internalized P3 was found associated with mitochondria, but contrary to the parental 2B protein, the short peptide did not affect the morphology or cell distribution of these organelles, nor induced apoptosis. We conclude that P3 constitutes a mitochondriotropic sequence, which is however devoid of 2B pro-apoptotic activity.
Keywords: Enterovirus 2B; Viroporin; Protein–lipid interaction; Pore-forming peptide; Viral protein-induced apoptosis
End-products diacylglycerol and ceramide modulate membrane fusion induced by a phospholipase C/sphingomyelinase from Pseudomonas aeruginosa by Maitane Ibarguren; Paul H.H. Bomans; Peter M. Frederik; Martin Stonehouse; Adriana I. Vasil; Michael L. Vasil; Alicia Alonso; Félix M. Goñi (pp. 59-64).
A phospholipase C/sphingomyelinase from Pseudomonas aeruginosa has been assayed on vesicles containing phosphatidylcholine, sphingomyelin, phosphatidylethanolamine and cholesterol at equimolar ratios. The enzyme activity modifies the bilayer chemical composition giving rise to diacylglycerol (DAG) and ceramide (Cer). Assays of enzyme activity, enzyme-induced aggregation and fusion have been performed. Ultrastructural evidence of vesicle fusion at various stages of the process is presented, based on cryo-EM observations. The two enzyme lipidic end-products, DAG and Cer, have opposite effects on the bilayer physical properties; the former abolishes lateral phase separation, while the latter generates a new gel phase [Sot et al., FEBS Lett. 582, 3230–3236 (2008)]. Addition of either DAG, or Cer, or both to the liposome mixture causes an increase in enzyme binding to the bilayers and a decrease in lag time of hydrolysis. These two lipids also have different effects on the enzyme activity, DAG enhancing enzyme-induced vesicle aggregation and fusion, Cer inhibiting the hydrolytic activity. These effects are explained in terms of the different physical properties of the two lipids. DAG increases bilayers fluidity and decreases lateral separation of lipids, thus increasing enzyme activity and substrate accessibility to the enzyme. Cer has the opposite effect mainly because of its tendency to sequester sphingomyelin, an enzyme substrate, into rigid domains, presumably less accessible to the enzyme.
Keywords: Abbreviations; Cer; egg ceramide; DAG; diacylglycerol; LUV; large unilamellar vesicles; NBD-PE; N-(7-nitrobenzen-2-oxa-1,3-diazol-4-ol)-phosphatidylethanola; PC; phosphatidylcholine; PE; phosphatidylethanolamine; PLC; phospholipase C; PlcHR; 2; phospholipase C/sphingomyelinase from; Pseudomonas aeruginosa; Rho-PE; rhodamine phosphatidylethanolamine; SM; sphingomyelinMembrane fusion; Phospholipase C; Sphingomyelinase; Diacylglycerol; Ceramide; Pseudomonas aeruginosa; PlcHR2