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Nature Reviews. Molecular Cell Biology Jun 2017Cellular plasma membranes are laterally heterogeneous, featuring a variety of distinct subcompartments that differ in their biophysical properties and composition. A... (Review)
Review
Cellular plasma membranes are laterally heterogeneous, featuring a variety of distinct subcompartments that differ in their biophysical properties and composition. A large number of studies have focused on understanding the basis for this heterogeneity and its physiological relevance. The membrane raft hypothesis formalized a physicochemical principle for a subtype of such lateral membrane heterogeneity, in which the preferential associations between cholesterol and saturated lipids drive the formation of relatively packed (or ordered) membrane domains that selectively recruit certain lipids and proteins. Recent studies have yielded new insights into this mechanism and its relevance in vivo, owing primarily to the development of improved biochemical and biophysical technologies.
Topics: Animals; Cell Membrane; Humans; Membrane Lipids; Membrane Microdomains
PubMed: 28356571
DOI: 10.1038/nrm.2017.16 -
Current Opinion in Lipidology Oct 2017Reception and transmission of signals across the plasma membrane has been a function generally attributed to transmembrane proteins. In the last 3 years, however, a... (Review)
Review
PURPOSE OF REVIEW
Reception and transmission of signals across the plasma membrane has been a function generally attributed to transmembrane proteins. In the last 3 years, however, a growing number of reports have further acknowledged important contributions played by membrane lipids in the process of signal transduction.
RECENT FINDINGS
In particular, the constituency of membrane lipids can regulate how proteins with SH2 domains and molecules like K-Ras expose their catalytic domains to the cytosol and interact with effectors and second messengers. Recent reports have also shown that the degree of saturation of phospholipids can reduce the activation of certain G-protein-coupled receptors, and signaling downstream to Toll-like receptor 4 with consequences to nuclear factor kappa B activation and inflammation. Levels of specific gangliosides in the membrane were reported to activate integrins in a cell-autonomous manner affecting tumor cell migration. Furthermore, high resolution of the association of cholesterol with the smoothened receptor has clarified its participation in sonic hedgehog signaling. These are some of the key advancements that have further propelled our understanding of the broad versatile contributions of membrane lipids in signal transduction.
SUMMARY
As we gain definitive detail regarding the impact of lipid-protein interactions and their consequences to cell function, the options for therapeutic targeting expand with the possibility of greater specificity.
Topics: Animals; Humans; Membrane Lipids; Membrane Microdomains; Membrane Proteins; Phospholipids; Signal Transduction
PubMed: 28692598
DOI: 10.1097/MOL.0000000000000443 -
Journal of Molecular Biology Dec 2016Biological membranes are complex and dynamic assemblies of lipids and proteins. Poikilothermic organisms including bacteria, fungi, reptiles, and fish do not control... (Review)
Review
Biological membranes are complex and dynamic assemblies of lipids and proteins. Poikilothermic organisms including bacteria, fungi, reptiles, and fish do not control their body temperature and must adapt their membrane lipid composition in order to maintain membrane fluidity in the cold. This adaptive response was termed homeoviscous adaptation and has been frequently studied with a specific focus on the acyl chain composition of membrane lipids. Massspectrometry-based lipidomics can nowadays provide more comprehensive insights into the complexity of lipid remodeling during adaptive responses. Eukaryotic cells compartmentalize biochemical processes in organelles with characteristic surface properties, and the lipid composition of organelle membranes must be tightly controlled in order to maintain organelle function and identity during adaptive responses. Some highly differentiated cells such as neurons maintain unique lipid compositions with specific physicochemical properties. To date little is known about the sensory mechanisms regulating the acyl chain profile in such specialized cells or during adaptive responses. Here we summarize our current understanding of lipid metabolic networks with a specific focus on the role of physicochemical membrane properties for the regulation of the acyl chain profile during homeoviscous adaptation. By comparing the mechanisms of the bacterial membrane sensors with the prototypical eukaryotic lipid packing sensor Mga2 fromSaccharomyces cerevisiae,we identify common operational principles that might guide our search for novel membrane sensors in different organelles, organisms, and highly specialized cells.
Topics: Adaptation, Physiological; Bacteria; Cell Membrane; Fungi; Homeostasis; Membrane Fluidity; Membrane Lipids; Metabolic Networks and Pathways; Models, Biological
PubMed: 27534816
DOI: 10.1016/j.jmb.2016.08.013 -
Current Topics in Membranes 2019The plasma membrane forms the physical barrier between the cytoplasm and extracellular space, allowing for biochemical reactions necessary for life to occur. Plasma... (Review)
Review
The plasma membrane forms the physical barrier between the cytoplasm and extracellular space, allowing for biochemical reactions necessary for life to occur. Plasma membrane damage needs to be rapidly repaired to avoid cell death. This relies upon the coordinated action of the machinery that polarizes the repair response to the site of injury, resulting in resealing of the damaged membrane and subsequent remodeling to return the injured plasma membrane to its pre-injury state. As lipids comprise the bulk of the plasma membrane, the acts of injury, resealing, and remodeling all directly impinge upon the plasma membrane lipids. In addition to their structural role in shaping the physical properties of the plasma membrane, lipids also play an important signaling role in maintaining plasma membrane integrity. While much attention has been paid to the involvement of proteins in the membrane repair pathway, the role of lipids in facilitating plasma membrane repair remains poorly studied. Here we will discuss the current knowledge of how lipids facilitate plasma membrane repair by regulating membrane structure and signaling to coordinate the repair response, and will briefly note how lipid involvement extends beyond plasma membrane repair to the tissue repair response.
Topics: Animals; Cell Membrane; Humans; Membrane Lipids; Molecular Structure; Signal Transduction
PubMed: 31610866
DOI: 10.1016/bs.ctm.2019.07.001 -
Chemical Reviews May 2021The outer membrane of Gram-negative bacteria is essential for their survival in harsh environments and provides intrinsic resistance to many antibiotics. This membrane... (Review)
Review
The outer membrane of Gram-negative bacteria is essential for their survival in harsh environments and provides intrinsic resistance to many antibiotics. This membrane is remarkable; it is a highly asymmetric lipid bilayer. The inner leaflet of the outer membrane contains phospholipids, whereas the fatty acyl chains attached to lipopolysaccharide (LPS) comprise the hydrophobic portion of the outer leaflet. This lipid asymmetry, and in particular the exclusion of phospholipids from the outer leaflet, is key to creating an almost impenetrable barrier to hydrophobic molecules that can otherwise pass through phospholipid bilayers. It has long been known that these lipids are not made in the outer membrane. It is now believed that conserved multisubunit protein machines extract these lipids after their synthesis is completed at the inner membrane and transport them to the outer membrane. A longstanding question is how the cell builds and maintains this asymmetric lipid bilayer in coordination with the assembly of the other components of the cell envelope. This Review describes the trans-envelope lipid transport systems that have been identified to participate in outer-membrane biogenesis: LPS transport via the Lpt machine, and phospholipid transport via the Mla pathway and several recently proposed transporters.
Topics: Bacterial Outer Membrane; Escherichia coli; Hydrophobic and Hydrophilic Interactions; Lipid Bilayers; Lipopolysaccharides; Membrane Lipids; Models, Molecular; Phospholipids
PubMed: 32955879
DOI: 10.1021/acs.chemrev.0c00587 -
Current Opinion in Chemical Biology Aug 2022Membrane proteins and lipids play roles in regulating biological functions of cells. However, the analysis of interactions between membrane proteins and lipids in... (Review)
Review
Membrane proteins and lipids play roles in regulating biological functions of cells. However, the analysis of interactions between membrane proteins and lipids in biological membranes remains challenging. Native membranes typically contain heterogenous lipid mixtures and low amounts of membrane proteins. This review presents recent developments in membrane mimetics and complementary mass spectrometry approaches for the investigation of membrane protein-lipid interactions after protein expression and purification. Furthermore, it is exemplified how delipidation knowledge on membrane mimetics can be used to gain insights into the role of lipids for protein structure and function. Because every technology has its strengths and weaknesses, it becomes apparent that integrated research approaches will facilitate the investigation of complex membrane environments in the future.
Topics: Biomimetics; Cell Membrane; Mass Spectrometry; Membrane Lipids; Membrane Proteins
PubMed: 35580377
DOI: 10.1016/j.cbpa.2022.102157 -
The Plant Journal : For Cell and... Jul 2021Lipid remodeling, defined herein as post-synthetic structural modifications of membrane lipids, play crucial roles in regulating the physicochemical properties of... (Review)
Review
Lipid remodeling, defined herein as post-synthetic structural modifications of membrane lipids, play crucial roles in regulating the physicochemical properties of cellular membranes and hence their many functions. Processes affected by lipid remodeling include lipid metabolism, membrane repair, cellular homeostasis, fatty acid trafficking, cellular signaling and stress tolerance. Glycerolipids are the major structural components of cellular membranes and their composition can be adjusted by modifying their head groups, their acyl chain lengths and the number and position of double bonds. This review summarizes recent advances in our understanding of mechanisms of membrane lipid remodeling with emphasis on the lipases and acyltransferases involved in the modification of phosphatidylcholine and monogalactosyldiacylglycerol, the major membrane lipids of extraplastidic and photosynthetic membranes, respectively. We also discuss the role of triacylglycerol metabolism in membrane acyl chain remodeling. Finally, we discuss emerging data concerning the functional roles of glycerolipid remodeling in plant stress responses. Illustrating the molecular basis of lipid remodeling may lead to novel strategies for crop improvement and other biotechnological applications such as bioenergy production.
Topics: Enzymes; Gene Expression Regulation, Plant; Membrane Lipids; Plant Cells; Plant Proteins; Plants; Triglycerides
PubMed: 33853198
DOI: 10.1111/tpj.15273 -
Chemical Reviews May 2019Cell membranes contain a large variety of lipid types and are crowded with proteins, endowing them with the plasticity needed to fulfill their key roles in cell... (Review)
Review
Cell membranes contain a large variety of lipid types and are crowded with proteins, endowing them with the plasticity needed to fulfill their key roles in cell functioning. The compositional complexity of cellular membranes gives rise to a heterogeneous lateral organization, which is still poorly understood. Computational models, in particular molecular dynamics simulations and related techniques, have provided important insight into the organizational principles of cell membranes over the past decades. Now, we are witnessing a transition from simulations of simpler membrane models to multicomponent systems, culminating in realistic models of an increasing variety of cell types and organelles. Here, we review the state of the art in the field of realistic membrane simulations and discuss the current limitations and challenges ahead.
Topics: Cell Membrane; Humans; Lipid Bilayers; Membrane Lipids; Membrane Proteins; Models, Biological; Molecular Dynamics Simulation
PubMed: 30623647
DOI: 10.1021/acs.chemrev.8b00460 -
FEBS Letters May 2007Membrane fusion of enveloped viruses with cellular membranes is mediated by viral glycoproteins (GP). Interaction of GP with cellular receptors alone or coupled to... (Review)
Review
Membrane fusion of enveloped viruses with cellular membranes is mediated by viral glycoproteins (GP). Interaction of GP with cellular receptors alone or coupled to exposure to the acidic environment of endosomes induces extensive conformational changes in the fusion protein which pull two membranes into close enough proximity to trigger bilayer fusion. The refolding process provides the energy for fusion and repositions both membrane anchors, the transmembrane and the fusion peptide regions, at the same end of an elongated hairpin structure in all fusion protein structures known to date. The fusion process follows several lipidic intermediate states, which are generated by the refolding process. Although the major principles of viral fusion are understood, the structures of fusion protein intermediates and their mode of lipid bilayer interaction, the structures and functions of the membrane anchors and the number of fusion proteins required for fusion, necessitate further investigations.
Topics: Animals; Cell Membrane; Humans; Membrane Fusion; Membrane Lipids; Models, Molecular; Protein Conformation; Viral Fusion Proteins
PubMed: 17320081
DOI: 10.1016/j.febslet.2007.01.093 -
Biochimica Et Biophysica Acta Sep 2015All molecular interactions that are relevant to cellular and molecular structures are electrical in nature but manifest in a rich variety of forms that each has its own... (Review)
Review
All molecular interactions that are relevant to cellular and molecular structures are electrical in nature but manifest in a rich variety of forms that each has its own range and influences on the net effect of how molecular species interact. This article outlines how electrical interactions between the protein and lipid membrane components underlie many of the activities of membrane function. Particular emphasis is placed on spatially localised behaviour in membranes involving modulation of protein activity and microdomain structure. The interactions between membrane lipids and membrane proteins together with their role within cell biology represent an enormous body of work. Broad conclusions are not easy given the complexities of the various systems and even consensus with model membrane systems containing two or three lipid types is difficult. By defining two types of broad lipid-protein interaction, respectively Type I as specific and Type II as more non-specific and focussing on the electrical interactions mostly in the extra-membrane regions it is possible to assemble broad rules or a consensus of the dominant features of the interplay between these two fundamentally important classes of membrane component. This article is part of a special issue entitled: Lipid-protein interactions.
Topics: Animals; Cell Membrane; Electric Conductivity; Humans; Lipid Bilayers; Membrane Lipids; Membrane Proteins; Models, Biological; Models, Molecular; Protein Conformation
PubMed: 25817548
DOI: 10.1016/j.bbamem.2015.03.017