Mechanism and regulation of the violaxanthin cycle: The role of antenna proteins and membrane lipids

The violaxanthin cycle describes the reversible conversion of violaxanthin to zeaxanthin via the intermediate antheraxanthin. This light-dependent xanthophyll conversion is essential for the adaptation of plants and algae to different light conditions and allows a reversible switch of photosynthetic light-harvesting complexes between a light-harvesting state under low light and a dissipative state under high light. The photoprotective functions of zeaxanthin have been intensively studied during the last decade, but much less attention has been directed to the mechanism and regulation of xanthophyll conversion. In this review, an overview is given on recent progress in the understanding of the role of (i) xanthophyll binding by antenna proteins and of (ii) the lipid properties of the thylakoid membrane in the regulation of xanthophyll conversion. The consequences of these findings for the mechanism and regulation of xanthophyll conversion in the thylakoid membrane will be discussed.     

The role of lipids in the biogenesis of integral membrane proteins

Most integral membrane proteins are cotranslationally inserted into the lipid bilayer. In prokaryotes, membrane insertion of the nascent chain takes place at the plasma membrane, whereas in eukaryotes insertion takes place into the endoplasmatic reticulum. In both kingdoms of life, however, the same membrane that acquaints the newly born membrane protein also synthesizes the bilayer lipids and thus ensures the balanced growth of the membrane as a whole. Recent evidence indicates that the lipid composition of the host membrane can determine the fate of the newborn membrane protein, as it can affect (1) the efficiency of translocation, (2) the topology of the resulting membrane protein, (3) its stability, (4) its assembly into oligomeric complexes, (5) its transport and sorting along the secretory pathway, and (6) its enzymatic activity. The lipid composition of the membrane thus can affect the biogenesis and function of integral membrane proteins at multiple steps along its biogenetic pathway. While understanding this interdependence between bilayer lipids and protein biogenesis is interesting in its own right, careful consideration of a potential host’s membrane lipid composition may also allow optimization of the yield and activity of membrane proteins that are expressed in a heterologous organism. Here, we review and discuss some examples that illustrate the interdependence between bilayer lipids and the biogenesis of integral membrane proteins.     

The functions of polarized water and membrane lipids: a rebuttal

In 1973, experimental evidence was reported in support of the view that water polarized in multilayers rather than simple lipid is responsible for the semipermeable properties of living cell membranes. The present article presents a full rebuttal to a subsequent attack on that view.     

The role of interferon-alpha in regulation of nervous system functions

The review analyses contemporary data on the role of the interferon-alpha in the central nervous systems. Interferon-alpha is one of the key polyfunctional cytokines providing integrative activity of the neuro-immuno-endocrine complex. The emphasis is made on the molecular mechanisms of anti-viral, anti-proliferative and neuromodulating actions of the interferon-alpha in the brain. Mechanisms of its involvement in regulation of pain, sleep, body temperature, circadian rhythms, food consumption etc. are considered. Based on the literature and our data we hypothesized a dose-dependent action of exogenous interferon-alpha on the nervous system. We suggest that optimal schemes of chronic application of small interferon-alpha doses can be more expedient for treatment of viral or oncologic diseases than large doses causing neuropsychiatric disorders.     

整合素的活化调控

整合素家族是介导细胞与细胞外基质作用的最主要分子,不仅可以识别细胞外环境将信号传到细胞内,还可以通过来自细胞内的信号调节整合素和配体的亲和力,这个过程也就是整合素的活化。本文主要阐述了整合素的活化在生理过程中的重要作用、整合素活性调节的结构基础以及细胞内的信号通路和结合蛋白对整合素活性的影响。     

The role of lipids in membrane insertion and translocation of bacterial proteins

Phospholipids are essential building blocks of membranes and maintain the membrane permeability barrier of cells and organelles. They provide not only the bilayer matrix in which the functional membrane proteins reside, but they also can play direct roles in many essential cellular processes. In this review, we give an overview of the lipid involvement in protein translocation across and insertion into the Escherichia coli inner membrane. We describe the key and general roles that lipids play in these processes in conjunction with the protein components involved. We focus on the Sec-mediated insertion of leader peptidase. We describe as well the more direct roles that lipids play in insertion of the small coat proteins Pf3 and M13. Finally, we focus on the role of lipids in membrane assembly of oligomeric membrane proteins, using the potassium channel KcsA as model protein. In all cases, the anionic lipids and lipids with small headgroups play important roles in either determining the efficiency of the insertion and assembly process or contributing to the directionality of the insertion process.     

The role of the membrane potential in chondrocyte volume regulation

Many cell types have significant negative resting membrane potentials (RMPs) resulting from the activity of potassium‐selective and chloride‐selective ion channels. In excitable cells, such as neurones, rapid changes in membrane permeability underlie the generation of action potentials. Chondrocytes have less negative RMPs and the role of the RMP is not clear. Here we examine the basis of the chondrocyte RMP and possible physiological benefits. We demonstrate that maintenance of the chondrocyte RMP involves gadolinium‐sensitive cation channels. Pharmacological inhibition of these channels causes the RMP to become more negative (100 µM gadolinium: ΔV_m = ?30 ± 4 mV). Analysis of the gadolinium‐sensitive conductance reveals a high permeability to calcium ions (PCa/PNa ≈80) with little selectivity between monovalent ions; similar to that reported elsewhere for TRPV5. Detection of TRPV5 by PCR and immunohistochemistry and the sensitivity of the RMP to the TRPV5 inhibitor econazole (ΔV_m = ?18 ± 3 mV) suggests that the RMP may be, in part, controlled by TRPV5. We investigated the physiological advantage of the relatively positive RMP using a mathematical model in which membrane stretch activates potassium channels allowing potassium efflux to oppose osmotic water uptake. At very negative RMP potassium efflux is negligible, but at more positive RMP it is sufficient to limit volume increase. In support of our model, cells clamped at ?80 mV and challenged with a reduced osmotic potential swelled approximately twice as much as cells at +10 mV. The positive RMP may be a protective adaptation that allows chondrocytes to respond to the dramatic osmotic changes, with minimal changes in cell volume. J. Cell. Physiol. 226: 2979–2986, 2011. © 2011 Wiley‐Liss, Inc.     

The role of membrane lipids in the induction of macrophage apoptosis by microparticles

Microparticles are membrane-derived vesicles that are released from cells during activation or cell death. These particles can serve as mediators of intercellular cross-talk and induce a variety of cellular responses. Previous studies have shown that macrophages undergo apoptosis after phagocytosing microparticles. Here, we have addressed the hypothesis that microparticles trigger this process via lipid pathways. In these experiments, microparticles induced apoptosis in primary macrophage cells or cell lines (RAW 264.7 or U937) with up to a 5-fold increase. Preincubation of macrophages with phosphatidylinositol-3,5-bisphosphate (PtdIns(3,5)BP) reduced the microparticle-induced apoptosis in a dose-dependent manner. PtdIns(3,5)BP is a specific inhibitor of the acid sphingomyelinase and thus can block the generation of pro-apoptotic ceramides. Similarly, the pre-incubation of macrophages with PtdIns(3,5)BP prevented microparticle-induced upregulation of caspase 8, which is a major target molecule of ceramide action in the apoptosis pathway. PtdIns(3,5)BP, however, had no effect on the spontaneous rate of apoptosis. To evaluate further signaling pathways induced by microparticles, the extracellular signal regulated kinase (ERK-) 1 was investigated. This kinase plays a role in activating phospholipases A2 which cleaves membrane phospholipids into arachidonic acid; microparticles have been suggested to be a preferred substrate for phospholipases A2. As shown in our experiments, microparticles strongly increased the amount of phosphorylated ERK1/2 in RAW 264.7 macrophages in a time-dependent manner, peaking 15 min after co-incubation. Addition of PD98059, a specific inhibitor of ERK1, prevented the increase in apoptosis of RAW 264.7 macrophages. Together, these data suggest that microparticles perturb lipid homeostasis of macrophages and thereby induce apoptosis. These results emphasize the importance of biolipids in the cellular cross-talk of immune cells. Based on the fact that in clinical situations with excessive cell death such as malignancies, autoimmune diseases and following chemotherapies high levels of circulating microparticles might modulate phagocytosing cells, a suppression of the immune response might occur due to loss of macrophages.     

The role of lipids in the regulation of ATP and PPi synthesis in mitochondria

It was demonstrated previously that mitochondria of higher and lower eukaryotes can synthesize, in the course of oxidative phosphorylation, not only ATP but also inorganic pyrophosphate (PPi). Two PPases were isolated from bovine heart mitochondria (soluble--PPase I and membrane--PPase II). Coupling PPase II, in contrast to PPase I, contains phosphatidyl choline, but PPase I is lipidized readily in the presence of different phospholipids. Reconstitution experiments of the PPi synthesis system have shown that after lipidization PPase I is able to incorporate into submitochondrial particles (SMP) and becomes a coupling factor for oxidation and PPi synthesis. It seems that phospholipid is indispensible for incorporation into the membrane and the manifestation of the coupling activity of the enzyme. The effect of lipids on the activity of soluble and membrane-bound pyrophosphatase was studied. It is shown that PPase II phospholipid is involved in the regulation of the hydrolase activity of the isolated enzyme. However, hydrolysis of PPi by SMP and its synthesis by mitochondria are affected by cooperative rearrangements of the entire lipid component of the membrane rather than by changes in the phase state of phosphatidyl choline contained in PPase II. An opposite response of ATP and PPi synthesis to changes in viscosity makes it likely that the viscosity of the mitochondrial inner membrane may control the levelling of these two processes in mitochondria.     

Progress in understanding the role of lipids in membrane protein folding

Detailed investigations of membrane protein folding present a number of serious technical challenges. Most studies addressing this subject have emphasized aspects of protein amino acid sequence and structure. While it is generally accepted that the interplay between proteins and lipids plays an important role in membrane protein folding, the role(s) played by membrane lipids in this process have only recently been explored in any detail. This review is intended to summarize recent studies in which particular lipids or membrane physical properties have been shown to play a role in the folding of intact, functionally competent integral membrane proteins. This article is part of a Special Issue entitled: Protein Folding in Membranes.     

Order from disorder, corralling cholesterol with chaotic lipids. The role of polyunsaturated lipids in membrane raft formation

A myriad of health benefits including the prevention of cancer and heart disease accompanies consumption of polyunsaturated fatty acids (PUFA). Of special importance is the omega-3-PUFA docosahexaenoic acid (DHA), with 22 carbons and six double bonds that constitute the most highly unsaturated fatty acid naturally occurring. Our experiments target the membrane as a likely site of action and focus upon the interaction of cholesterol with PUFA-containing phospholipids. They support the idea that steric incompatibility of the rigid steroid moiety for highly disordered PUFA chains promotes lateral segregation of lipids into PUFA-rich/sterol-poor and PUFA-poor/sterol-rich regions. Solid state 2H NMR and X-ray diffraction demonstrate that the solubility of cholesterol is low in polyunsaturated bilayers. In mixed membranes of phosphatidylethanolamine (PE) with the lipid raft-forming molecules sphingomyelin (SM) and cholesterol, diminished affinity of the sterol for 1-[2H31]palmitoyl-2-docosahexaenoylphosphatidylethanolamine ([2H31]16:0-22:6PE) relative to 1-[2H31]palmitoyl-2-oleoylphosphatidylethanolamine ([2H31]16:0-18:1PE) is identified by 2H NMR order parameters. Here, lies the origin of a potential biological advantage of the relatively modest increase in PUFA content of plasma membranes that would be conferred by dietary supplementation. We hypothesize that the enhanced propensity to form SM-/cholesterol-rich rafts as well as PUFA-rich/cholesterol-poor microdomains would modify the function of proteins for which these respective regions provide a platform.     

Phosphatidylglycerol and sulfoquinovosyldiacylglycerol: anionic membrane lipids and phosphate regulation

Photosynthetic membranes of organisms from cyanobacteria to seed plants are characterized by the neutral galactolipids and the anionic glycerolipids sulfoquinovosyldiacylglycerol and phosphatidylglycerol. Recent findings have brought new insights into the biosynthesis of the anionic membrane lipids, the evolutionary origin of the enzymes involved in this process, and the importance of phosphatidylglycerol and sulfoquinovosyldiacylgycerol in photosynthesis. Photosynthetic membranes require a defined level of anionic membrane lipids for proper function, and phosphatidylglycerol and sulfoquinovosyldiacylglycerol can substitute for each other to a certain extent. A defined level of phosphatidylglycerol is, however, indispensable for photoautotrophic growth. On the other hand, sulfoquinovosyldiacylglycerol plays a conditionally important role in enabling photosynthetic organisms to survive the phosphate-limiting conditions frequently encountered in natural habitats.