共查询到20条相似文献,搜索用时 15 毫秒
1.
Intracellular organelles, including endosomes, show differences not only in protein but also in lipid composition. It is becoming clear from the work of many laboratories that the mechanisms necessary to achieve such lipid segregation can operate at very different levels, including the membrane biophysical properties, the interactions with other lipids and proteins, and the turnover rates or distribution of metabolic enzymes. In turn, lipids can directly influence the organelle membrane properties by changing biophysical parameters and by recruiting partner effector proteins involved in protein sorting and membrane dynamics. In this review, we will discuss how lipids are sorted in endosomal membranes and how they impact on endosome functions.It is now well established that membranes along the endocytic and secretory pathway show differences not only in protein but also in lipid composition. For example, lipid gradients exist along the biosynthetic pathway with increasing density of cholesterol and sphingolipids from the endoplasmic reticulum (ER) to the plasma membrane (Maxfield and van Meer 2010). Also, phosphoinositides show distributions restricted to relatively well-characterized membrane territories (Di Paolo and De Camilli 2006). Given the facts that lipids are small and contain little structural information when compared with proteins, that they can diffuse rapidly within membranes, and that membranes are connected by membrane flow during transport, it is not always obvious how different lipids are segregated from each other.In this article, we will evoke different mechanisms that may contribute to the heterogeneous lipid composition of endocytic membranes, including physicochemical properties of the membrane, interactions with other proteins or lipids, and synthesis or degradation. In addition, it has also become apparent that peripheral membrane proteins often interact with membranes via diverse lipid-binding motifs, and thus that lipids directly contribute to the distribution of many peripheral membrane proteins. For example, phosphatidylinositol 3-phosphate (PI(3)P) is detected predominantly on early endosomes, where most characterized PI(3)P-binding proteins encoded by the human genome are found as well (Raiborg et al. 2013). We will also discuss how some lipids may regulate protein sorting and membrane transport within the endosomal system. 相似文献
2.
Lipids in eukaryotic cell membranes have been shown to cluster in "rafts" with different lipid/protein compositions and molecular packing. Model membranes such as giant unilamellar vesicles (GUVs) provide a key system to elucidate the physical mechanisms of raft assembly. Despite the large amount of work devoted to the detection and characterization of rafts, one of the most important pieces of information still missing in the picture of the cell membrane is dynamics: how lipids organize and move in rafts and how they modulate membrane fluidity. This missing element is of crucial importance for the trafficking at and from the periphery of the cell regulated by endo- and exocytosis and, in general, for the constant turnover which redistributes membrane components. Here, we review studies of combined confocal fluorescence microscopy and fluorescence correlation spectroscopy on lipid dynamics and organization in rafts assembled in GUVs prepared from various lipid mixtures which are relevant to the problem of raft formation. 相似文献
3.
Matthew?J. Justice Daniela?N. Petrusca Adriana?L. Rogozea Justin?A. Williams Kelly?S. Schweitzer Irina Petrache Stephen?R. Wassall Horia?I. Petrache 《Biophysical journal》2014,106(3):598-609
The engulfment function of macrophages relies on complex molecular interactions involving both lipids and proteins. In particular, the clearance of apoptotic bodies (efferocytosis) is enabled by externalization on the cell target of phosphatidylserine lipids, which activate receptors on macrophages, suggesting that (local) specific lipid-protein interactions are required at least for the initiation of efferocytosis. However, in addition to apoptotic cells, macrophages can engulf foreign bodies that vary substantially in size from a few nanometers to microns, suggesting that nonspecific interactions over a wide range of length scales could be relevant. Here, we use model lipid membranes (made of phosphatidylcholine, phosphatidylserine, and ceramide) and rat alveolar macrophages to show how lipid bilayer properties probed by small-angle x-ray scattering and solid-state 2H NMR correlate with engulfment rates measured by flow cytometry. We find that engulfment of protein-free model lipid vesicles is promoted by the presence of phosphatidylserine lipids but inhibited by ceramide, in accord with a previous study of apoptotic cells. We conclude that the roles of phosphatidylserine and ceramide in phagocytosis is based, at least in part, on lipid-mediated modification of membrane physical properties, including interactions at large length scales as well as local lipid ordering and possible domain formation. 相似文献
4.
Matthew J. Justice Daniela N. Petrusca Adriana L. Rogozea Justin A. Williams Kelly S. Schweitzer Irina Petrache Stephen R. Wassall Horia I. Petrache 《Biophysical journal》2014
The engulfment function of macrophages relies on complex molecular interactions involving both lipids and proteins. In particular, the clearance of apoptotic bodies (efferocytosis) is enabled by externalization on the cell target of phosphatidylserine lipids, which activate receptors on macrophages, suggesting that (local) specific lipid-protein interactions are required at least for the initiation of efferocytosis. However, in addition to apoptotic cells, macrophages can engulf foreign bodies that vary substantially in size from a few nanometers to microns, suggesting that nonspecific interactions over a wide range of length scales could be relevant. Here, we use model lipid membranes (made of phosphatidylcholine, phosphatidylserine, and ceramide) and rat alveolar macrophages to show how lipid bilayer properties probed by small-angle x-ray scattering and solid-state 2H NMR correlate with engulfment rates measured by flow cytometry. We find that engulfment of protein-free model lipid vesicles is promoted by the presence of phosphatidylserine lipids but inhibited by ceramide, in accord with a previous study of apoptotic cells. We conclude that the roles of phosphatidylserine and ceramide in phagocytosis is based, at least in part, on lipid-mediated modification of membrane physical properties, including interactions at large length scales as well as local lipid ordering and possible domain formation. 相似文献
5.
Lipid signaling 总被引:5,自引:0,他引:5
Wang X 《Current opinion in plant biology》2004,7(3):329-336
Various lipids are involved in mediating plant growth, development and responses to biotic and abiotic cues, and their production is regulated by lipid-signaling enzymes. Lipid-hydrolyzing enzymes play a pivotal role both in the production of lipid messengers and in other processes, such as cytoskeletal rearrangement, membrane trafficking, and degradation. Studies on the downstream targets and modes of action of lipid signals in plants are still in their early stages but distinguishing features of plant lipid-based signaling are being recognized. Phospholipase D enzymes and phosphatidic acid may play a broader role in lipid signaling in plants than in other systems. 相似文献
6.
Ben de Kruijff 《Current opinion in chemical biology》1997,1(4):564-569
In recent years, several major developments have taken place in the biology, physical chemistry and technology of polymorphism of membrane lipids. These include the identification of polymorphic regulation of membrane lipid composition in Escherichia coli, the importance of nonbilayer lipids for protein functioning, the special packing properties of bilayers containing these lipids, and the crystalization of a membrane protein out of three dimensional bilayer networks (lipid cubic phases). These exciting developments bring us closer to understanding the paradox of the lipid bilayer structure of biomembranes and the molecular basis of membrane protein structure and function. 相似文献
7.
Lipid rafts and the regulation of exocytosis 总被引:13,自引:0,他引:13
Exocytosis is the process whereby intracellular fluid-filled vesicles fuse with the plasma membrane, incorporating vesicle proteins and lipids into the plasma membrane and releasing vesicle contents into the extracellular milieu. Exocytosis can occur constitutively or can be tightly regulated, for example, neurotransmitter release from nerve endings. The last two decades have witnessed the identification of a vast array of proteins and protein complexes essential for exocytosis. SNARE proteins fill the spotlight as probable mediators of membrane fusion, whereas proteins such as munc18/nsec1, NSF and SNAPs function as essential SNARE regulators. A central question that remains unanswered is how exocytic proteins and protein complexes are spatially regulated. Recent studies suggest that lipid rafts, cholesterol and sphingolipid-rich microdomains, enriched in the plasma membrane, play an essential role in regulated exocytosis pathways. The association of SNAREs with lipid rafts acts to concentrate these proteins at defined sites of the plasma membrane. Furthermore, cholesterol depletion inhibits regulated exocytosis, suggesting that lipid raft domains play a key role in the regulation of exocytosis. This review examines the role of lipid rafts in regulated exocytosis, from a passive role as spatial coordinator of exocytic proteins to a direct role in the membrane fusion reaction. 相似文献
8.
J.A. Poveda A.M. GiudiciM.L. Renart M.L. MolinaE. Montoya A. Fernández-CarvajalG. Fernández-Ballester J.A. EncinarJ.M. González-Ros 《生物化学与生物物理学报:生物膜》2014
Ion channel conformational changes within the lipid membrane are a key requirement to control ion passage. Thus, it seems reasonable to assume that lipid composition should modulate ion channel function. There is increasing evidence that this implicates not just an indirect consequence of the lipid influence on the physical properties of the membrane, but also specific binding of selected lipids to certain protein domains. The result is that channel function and its consequences on excitability, contractility, intracellular signaling or any other process mediated by such channel proteins, could be subjected to modulation by membrane lipids. From this it follows that development, age, diet or diseases that alter lipid composition should also have an influence on those cellular properties. The wealth of data on the non-annular lipid binding sites in potassium channel from Streptomyces lividans (KcsA) makes this protein a good model to study the modulation of ion channel structure and function by lipids. The fact that this protein is able to assemble into clusters through the same non-annular sites, resulting in large changes in channel activity, makes these sites even more interesting as a potential target to develop lead compounds able to disrupt such interactions and hopefully, to modulate ion channel function. This Article is Part of a Special Issue Entitled: Membrane Structure and Function: Relevance in the Cell's Physiology, Pathology and Therapy. 相似文献
9.
Gibbs AG 《Journal of insect physiology》2002,48(4):391-400
The idea that the physical properties of cuticular lipids affect cuticular permeability goes back over 65 years. This proposal has achieved textbook status, despite controversy and the general lack of direct supporting evidence. Recent work supports the standard model, in which lipid melting results in increased cuticular permeability. Surprisingly, although all species studied to date can synthesize lipids that remain in a solid state at environmental temperatures, partial melting often occurs due to the deposition of lipids with low melting points. This will tend to increase water loss; the benefits may include better dispersal of lipids or other compounds across the cuticle or improved communication via cuticular pheromones. In addition, insects with high melting-point lipids are not necessarily less permeable at low temperatures. One likely reason is variation in lipid properties within the cuticle. Surface lipids differ from one region to another, and biophysical studies of model mixtures suggest the occurrence of phase separation between melted and solid lipid fractions. Lipid phase separation may have important implications for insect water balance and chemical communication. 相似文献
10.
《Biophysical journal》2021,120(24):5619-5630
Cryopreservation of oocytes has already been used to preserve genetic resources, but this technology faces limitations when applied to the species whose oocytes contain large amounts of cytoplasmic lipid droplets. Although cryoinjuries in such oocytes are usually associated with the lipid phase transition in lipid droplets, this phenomenon is still poorly understood. We applied Raman spectroscopy of deuterium-labeled lipids to investigate the freezing of lipid droplets inside cat oocytes. Lipid phase separation was detected in oocytes cryopreserved by slow-freezing protocol. For oocytes supplemented with stearic acid, we found that saturated lipids form the ordered phase being distributed at the periphery of lipid droplets. When an oocyte is warmed to physiological temperatures after cooling, a fraction of saturated lipids may remain in the ordered conformational state. The fractions of monounsaturated and polyunsaturated lipids redistribute to the core of lipid droplets. Monounsaturated lipids undergo the transition to the ordered conformational state below −10°C. Using deuterated fatty acids with a different number of double bonds, we reveal how different lipid fractions are involved in the lipid phase transition of a cytoplasmic lipid droplet and how they can affect cell survival. Raman spectroscopy of deuterated lipids has proven to be a promising tool for studying the lipid phase transitions and lipid redistributions inside single organelles within living cells. 相似文献
11.
Aurélien Bour Sergei G. Kruglik Morgan Chabanon Padmini Rangamani Nicolas Puff Stephanie Bonneau 《Biophysical journal》2019,116(5):910-920
Unsaturated lipid oxidation is a fundamental process involved in different aspects of cellular bioenergetics; dysregulation of lipid oxidation is often associated with cell aging and death. To study how lipid oxidation affects membrane biophysics, we used a chlorin photosensitizer to oxidize vesicles of various lipid compositions and degrees of unsaturation in a controlled manner. We observed different shape transitions that can be interpreted as an increase in the area of the targeted membrane followed by a decrease. These area modifications induced by the chemical modification of the membrane upon oxidation were followed in situ by Raman tweezers microspectroscopy. We found that the membrane area increase corresponds to the lipids’ peroxidation and is initiated by the delocalization of the targeted double bonds in the tails of the lipids. The subsequent decrease of membrane area can be explained by the formation of cleaved secondary products. As a result of these area changes, we observe vesicle permeabilization after a time lag that is characterized in relation with the level of unsaturation. The evolution of photosensitized vesicle radius was measured and yields an estimation of the mechanical changes of the membrane over oxidation time. The membrane is both weakened and permeabilized by the oxidation. Interestingly, the effect of unsaturation level on the dynamics of vesicles undergoing photooxidation is not trivial and thus carefully discussed. Our findings shed light on the fundamental dynamic mechanisms underlying the oxidation of lipid membranes and highlight the role of unsaturations on their physical and chemical properties. 相似文献
12.
Yuansong Bai Lingjun Meng Leng Han Yuanyuan Jia Yanan Zhao Huan Gao Rui Kang Xiaofeng Wang Daolin Tang Enyong Dai 《Biochemical and biophysical research communications》2019,508(4):997-1003
The synthesis, storage, and degradation of lipids are highly regulated processes. Impaired lipid metabolism is implicated in inflammation and cell death. Although ferroptosis is a recently described form of regulated cell death driven by lipid peroxidation, the impact of lipid droplets on ferroptosis remains unidentified. Here, we demonstrate that lipophagy, the autophagic degradation of intracellular lipid droplets, promotes RSL3-induced ferroptotic cell death in hepatocytes. Lipid droplet accumulation is increased at the early stage but decreased at the late stage of ferroptosis in mouse or human hepatocytes. Importantly, either genetically enhancing TPD52-dependent lipid storage or blocking ATG5-and RAB7A-dependent lipid degradation prevents RSL3-induced lipid peroxidation and subsequent ferroptosis in vitro and in vivo. These studies support an antioxidant role for lipid droplets in cell death and suggest novel strategies for the inhibition of ferroptosis by targeting the lipophagy pathway. 相似文献
13.
Lipid rafts: bringing order to chaos 总被引:27,自引:0,他引:27
Pike LJ 《Journal of lipid research》2003,44(4):655-667
Lipid rafts are subdomains of the plasma membrane that contain high concentrations of cholesterol and glycosphingolipids. They exist as distinct liquid-ordered regions of the membrane that are resistant to extraction with nonionic detergents. Rafts appear to be small in size, but may constitute a relatively large fraction of the plasma membrane. While rafts have a distinctive protein and lipid composition, all rafts do not appear to be identical in terms of either the proteins or the lipids that they contain. A variety of proteins, especially those involved in cell signaling, have been shown to partition into lipid rafts. As a result, lipid rafts are thought to be involved in the regulation of signal transduction. Experimental evidence suggests that there are probably several different mechanisms through which rafts control cell signaling. For example, rafts may contain incomplete signaling pathways that are activated when a receptor or other required molecule is recruited into the raft. Rafts may also be important in limiting signaling, either by physical sequestration of signaling components to block nonspecific interactions, or by suppressing the intrinsic activity of signaling proteins present within rafts. This review provides an overview of the physical characteristics of lipid rafts and summarizes studies that have helped to elucidate the role of lipid rafts in signaling via receptor tyrosine kinases and G protein-coupled receptors. 相似文献
14.
HUGO D. LUJAN MICHAEL R. MOWATT THEODORE E. NASH 《The Journal of eukaryotic microbiology》1996,43(3):237-242
To better understand the lipid requirements of Giardia lamblia trophozoites and the mechanisms of lipid uptake, we supplemented serum-free TYI-S-33 medium with lipids incorporated into different lipid carriers. We found that serum lipoproteins, β-cyclodextrins, and bile salts are able to supply cholesterol and phospholipids to Giardia and to support the multiplication of the parasite in vitro. The growth rates obtained with different lipoproteins or bile salts and lipid mixtures were similar to that in standard culture medium containing serum. Pulse labelling experiments using fluorescent lipid analogs demonstrated that Giardia can take up lipids from lipoproteins, β-cyclodextrins, or bile salt micelles, but with different kinetics, and that bile salts greatly facilitated lipid transfer from lipoproteins and cyclodextrins to the parasite surface. The binding of different radioiodinated lipoprotein classes to the trophozoite surface, inhibition of lipoprotein interiorization at 4°C or by cytochalasin D, and incorporation studies using fluorescent LDL suggested that a small component of lipid uptake by trophozoites was likely due to endocytosis of lipoproteins. 相似文献
15.
Measurement of the time-resolved fluorescence depolarization of 1,6-diphenylhexatriene (DPH) in artificial bilayers of microsomal membrane lipids from Tetrahymena gives detailed information concerning the molecular motion of this probe and fluid properties of the membrane lipids which are obscured with steady-state methods. The rotational motion of DPH in these lipids from cells acclimated to 15 and 39.5 degrees C growth temperatures was anisotropic, which agrees with recent time-resolved studies of this probe in synthetic phospholipid systems. Evaluation of DPH polarization data obtained from these lipid fractions at their respective growth temperatures showed differences in physical properties which suggest that "viscosity", per se, of the microsomal lipids is not a strictly regulated as it is in prokaryotic systems. Rotational relaxation of DPH in 39.5 degrees C microsomal lipids measured at 15 degrees C is more complex than that of either lipid fraction measured at its actual growth temperature, suggesting that the probe has partitioned into two dissimilar environments within the bilayer. Similar effects are observed in the microsomes of 39.5 degrees C cells by freeze-fracture electron microscopy following rapid cooling to 15 degrees C. Under these conditions, two distinct regions are observed on the fracture faces, suggesting a correlation between lipid phase changes and alterations in membrane structure. 相似文献
16.
Leidy C Gousset K Ricker J Wolkers WF Tsvetkova NM Tablin F Crowe JH 《Cell biochemistry and biophysics》2004,40(2):123-148
Lipid domains are acquiring increasing importance in our understanding of the regulation of several key functions in living
cells. We present here a discussion of the physical mechanisms driving the phase separation of membrane lipid components that
make up these domains, including phase behavior of the lipids and the role of cholesterol. In addition, we discuss phenomena
that regulate domain geometry and dimensions. We present evidence that these mechanisms apply to the regulation of domains
in intact cells. For example, the observation that physiologically functional microdomains present at 37°C aggregate into
macrodomains in human blood platelets when they are chilled below membrane lipid phase transition temperatures is predictable
from the known behavior of the constituent lipids in vitro. Finally, we show that the principles developed from studies on
these lipids in model systems can be used to develop techniques to stabilize the physiological, resting microdomain structure
of platelets during freeze-drying. These latter findings have immediate applications in clinical medicine for the development
of methods for storing platelets for therapeutic use. 相似文献
17.
ADIPOSE TISSUE : Morphological Changes Associated with Lipid Mobilization 总被引:17,自引:13,他引:4
下载免费PDF全文
![点击此处可从《The Journal of cell biology》网站下载免费的PDF全文](/ch/ext_images/free.gif)
Joseph R. Williamson 《The Journal of cell biology》1964,20(1):57-74
Morphological changes associated with mobilization of lipid were studied in epididymal adipose tissue from fasted and from alloxan diabetic rats. In both groups of animals a decrease in lipid content was accompanied by the formation of complex frond-like cytoplasmic processes and of loops and folds of basement membrane which extended from cell surfaces. These changes, evident after 1 day of fasting, increased in magnitude with increasing weight loss. As the lipid content of the cell decreased further, lipid-cytoplasmic interfaces became irregular and convoluted. Cytoplasmic microvesicles were prominent and appeared to be greatly increased in number. Rosette-like structures composed of microvesicles were observed in both lipid-depleted fat cells and endothelium. The interpretation of these changes and their physiological significance are discussed in terms of the physical and chemical properties of lipids and lipid metabolism. It is postulated that microvesicles may represent the mechanism of transport of free fatty acids in fat cells and in endothelium. Hypotheses are proposed and illustrated schematically for the mode of formation of microvesicular rosettes, for the mobilization and uptake of lipids by fat cells, and for the transport of lipids through endothelium. 相似文献
18.
《Biochimica et Biophysica Acta (BBA)/Molecular and Cell Biology of Lipids》2020,1865(1):158461
Structural lipids are mostly synthesized in the endoplasmic reticulum (ER), from which they are actively transported to the membranes of other organelles. Lipids can leave the ER through vesicular trafficking or non-vesicular lipid transfer and, curiously, both processes can be regulated either by the transported lipid cargos themselves or by different secondary lipid species. For most structural lipids, transport out of the ER membrane is a key regulatory component controlling their synthesis. Distribution of the lipids between the two leaflets of the ER bilayer or between the ER and other membranes is also critical for maintaining the unique membrane properties of each cellular organelle. How cells integrate these processes within the ER depends on fine spatial segregation of the molecular components and intricate metabolic channeling, both of which we are only beginning to understand. This review will summarize some of these complex processes and attempt to identify the organizing principles that start to emerge. This article is part of a Special Issue entitled Endoplasmic reticulum platforms for lipid dynamics edited by Shamshad Cockcroft and Christopher Stefan. 相似文献
19.
Corrie J. B. daCosta Sarah A. Medaglia Nadine Lavigne Shuzhi Wang Casey L. Carswell John E. Baenziger 《The Journal of biological chemistry》2009,284(49):33841-33849
Anionic lipids influence the ability of the nicotinic acetylcholine receptor to gate open in response to neurotransmitter binding, but the underlying mechanisms are poorly understood. We show here that anionic lipids with relatively small headgroups, and thus the greatest ability to influence lipid packing/bilayer physical properties, are the most effective at stabilizing an agonist-activatable receptor. The differing abilities of anionic lipids to stabilize an activatable receptor stem from differing abilities to preferentially favor resting over both uncoupled and desensitized conformations. Anionic lipids thus modulate multiple acetylcholine receptor conformational equilibria. Our data suggest that both lipids and membrane physical properties act as classic allosteric modulators influencing function by interacting with and thus preferentially stabilizing different native acetylcholine receptor conformational states. 相似文献
20.
Cultivation of Acholeplasma laidlawii cells in media containing unsaturated fatty acids results in changes of the physiological state of the membrane lipid bilayer due to preferable incorporation of an unsaturated fatty acid into lipids. The lipids are capable to regulate the transport activity since the transport rates for glucose, 3-O-methyl-C-glucose, glucerol and erythritol change considerably when the cells are cultivated in media containing different unsaturated fatty acids. The transport activity is also affected by the length of the carbon chain, the degree of the fatty acid saturation and the presence of cholesterol. At the same time the activation energy of the transport activity also changes, which suggests that the regulation by lipids (presumably local changes of the physical properties of lipid domen) is involved in the process of the carrier association with the substrate and/or in translocation of this complex through the membrane. 相似文献