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Chemistry and Physics of Lipids Jul 2023Labyrinthopeptins constitute a class of ribosomal synthesized peptides belonging to the type III family of lantibiotics. They exist in different variants and display...
Labyrinthopeptins constitute a class of ribosomal synthesized peptides belonging to the type III family of lantibiotics. They exist in different variants and display broad antiviral activities as well as show antiallodynic activity. Although their mechanism of action is not understood, it has been described that Labyrinthopeptins interact with membrane phospholipids modulating its biophysical properties and point out to membrane destabilization as its main point of action. We have used all-atom molecular dynamics to study the location of labyrinthopeptin A2 in a complex membrane as well as the existence of specific interactions with membrane lipids. Our results indicate that labyrinthopeptin A2, maintaining its globular structure, tends to be placed at the membrane interface, mainly between the phosphate atoms of the phospholipids and the oxygen atom of cholesterol modulating the biophysical properties of the membrane lipids. Outstandingly, we have found that labyrinthopeptin A2 tends to be preferentially surrounded by sphingomyelin while excluding cholesterol. The bioactive properties of labyrinthopeptin A2 could be attributed to the specific disorganization of raft domains in the membrane and the concomitant disruption of the overall membrane organization. These results support the improvement of Labyrinthopeptins as therapeutic molecules, opening up new opportunities for future medical advances.
Topics: Membrane Lipids; Phospholipids; Bacteriocins; Cholesterol; Membrane Microdomains
PubMed: 37061155
DOI: 10.1016/j.chemphyslip.2023.105303 -
Current Opinion in Plant Biology Dec 2017During plant-microbe interactions, host cells need to keep stringent control over the approaching pathogens and symbionts. This requires specific spatio-temporal... (Review)
Review
During plant-microbe interactions, host cells need to keep stringent control over the approaching pathogens and symbionts. This requires specific spatio-temporal assemblies of pattern recognition receptors and other complex constituents and a strict physical separation of genetically overlapping pathways. Increasing evidence suggests that this is, at least partially, achieved by the formation of nanometer scale membrane platforms that might act as signaling hubs. These and other larger-scale sub-compartments have been termed 'membrane rafts', 'nanodomains' and 'microdomains'. This review focuses on recent advances in understanding these nano-scale signaling platforms during plant-microbe interactions and proposes a common definition meant to facilitate the precise discrimination between different types of membrane domains in the future.
Topics: Bacterial Physiological Phenomena; Host-Pathogen Interactions; Membrane Microdomains; Plants; Signal Transduction; Symbiosis
PubMed: 28865975
DOI: 10.1016/j.pbi.2017.08.008 -
Biochimica Et Biophysica Acta Apr 2016Glycosylphosphatidylinositol (GPI)-anchored proteins (GPI-APs) are a class of membrane proteins containing a soluble protein attached by a conserved glycolipid anchor to... (Review)
Review
Glycosylphosphatidylinositol (GPI)-anchored proteins (GPI-APs) are a class of membrane proteins containing a soluble protein attached by a conserved glycolipid anchor to the external leaflet of the plasma membrane. In polarized epithelial cells, GPI-APs are predominantly sorted to the apical surface in the trans-Golgi network (TGN) by clustering in sphingolipid- and cholesterol-dependent microdomains (or rafts), which have been proposed to act as apical sorting platforms. Recent data indicate that the mechanisms of GPI-AP sorting, occurring in the Golgi, control both the membrane transport of GPI-APs and their specific activity at the apical surface of fully polarized epithelial cells. Here, we discuss the most recent findings and the factors regulating apical sorting of GPI-APs at the Golgi in polarized epithelial cells. We also underline the differences in the plasma membrane organization of GPI-APs between polarized and non-polarized cells supporting the existence of various mechanisms that control GPI-AP organization in different cell types.
Topics: Cell Membrane; Cell Polarity; Cholesterol; Epithelial Cells; Glycosylphosphatidylinositols; Humans; Membrane Microdomains; Membrane Proteins; Protein Transport; trans-Golgi Network
PubMed: 26706096
DOI: 10.1016/j.bbamem.2015.12.018 -
Chemical Society Reviews May 2021Systematically dissecting the molecular basis of the cell surface as well as its related biological activities is considered as one of the most cutting-edge fields in... (Review)
Review
Systematically dissecting the molecular basis of the cell surface as well as its related biological activities is considered as one of the most cutting-edge fields in fundamental sciences. The advent of various advanced cell imaging techniques allows us to gain a glimpse of how the cell surface is structured and coordinated with other cellular components to respond to intracellular signals and environmental stimuli. Nowadays, cell surface-related studies have entered a new era featured by a redirected aim of not just understanding but artificially manipulating/remodeling the cell surface properties. To meet this goal, biologists and chemists are intensely engaged in developing more maneuverable cell surface labeling strategies by exploiting the cell's intrinsic biosynthetic machinery or direct chemical/physical binding methods for imaging, sensing, and biomedical applications. In this review, we summarize the recent advances that focus on the visualization of various cell surface structures/dynamics and accurate monitoring of the microenvironment of the cell surface. Future challenges and opportunities in these fields are discussed, and the importance of cell surface-based studies is highlighted.
Topics: Animals; Cell Membrane; Fluorescent Dyes; Humans; Membrane Microdomains; Metabolic Engineering; Microscopy, Fluorescence; Polysaccharides; Staining and Labeling; Surface Properties
PubMed: 34027939
DOI: 10.1039/d1cs00067e -
Neurologia 2023Rafts are protein-lipid structural nanodomains involved in efficient signal transduction and the modulation of physiological processes of the cell plasma membrane. Raft... (Review)
Review
INTRODUCTION
Rafts are protein-lipid structural nanodomains involved in efficient signal transduction and the modulation of physiological processes of the cell plasma membrane. Raft disruption in the nervous system has been associated with a wide range of disorders.
DEVELOPMENT
We review the concept of rafts, the nervous system processes in which they are involved, and their role in diseases such as Parkinson's disease, Alzheimer disease, and Huntington disease.
CONCLUSIONS
Based on the available evidence, preservation and/or reconstitution of rafts is a promising treatment strategy for a wide range of neurological disorders.
Topics: Humans; Caveolae; Membrane Microdomains; Cholesterol; Cell Membrane; Alzheimer Disease
PubMed: 37858892
DOI: 10.1016/j.nrleng.2023.10.003 -
Biochemistry. Biokhimiia Feb 2020Exosomes (secreted extracellular vesicles formed in the intracellular vesicular transport system) play a crucial role in distant cell-cell communication. Exosomes... (Review)
Review
Exosomes (secreted extracellular vesicles formed in the intracellular vesicular transport system) play a crucial role in distant cell-cell communication. Exosomes transfer active forms of various biomolecules; the molecular composition of the exosomal cargo is a result of targeted selection and depends on the type of producer cells. The mechanisms underlying exosome formation and cargo selection are poorly understood. It is believed that there are several pathways for exosome biogenesis, although the questions about their independence and simultaneous coexistence in the cell still remain open. The least studied topic is the recently discovered mechanism of exosome formation associated with lipid rafts, or membrane lipid microdomains. Here, we present modern concepts and basic hypotheses on the mechanisms of exosome biogenesis and secretion and summarize current data on the involvement of lipid rafts and their constituent molecules in these processes. Special attention is paid to the analysis of possible role in the exosome formation of raft-forming proteins of the SPFH family, components of planar rafts, and caveolin, the main component of caveolae.
Topics: Animals; Exosomes; Humans; Membrane Microdomains
PubMed: 32093594
DOI: 10.1134/S0006297920020054 -
Development (Cambridge, England) Jun 2016The membranes of eukaryotic cells create hydrophobic barriers that control substance and information exchange between the inside and outside of cells and between... (Review)
Review
The membranes of eukaryotic cells create hydrophobic barriers that control substance and information exchange between the inside and outside of cells and between cellular compartments. Besides their roles as membrane building blocks, some membrane lipids, such as phosphoinositides (PIs), also exert regulatory effects. Indeed, emerging evidence indicates that PIs play crucial roles in controlling polarity and growth in plants. Here, I highlight the key roles of PIs as important regulatory membrane lipids in plant development and function.
Topics: Membrane Microdomains; Models, Biological; Phosphatidylinositols; Plant Development; Plants; Signal Transduction
PubMed: 27302395
DOI: 10.1242/dev.136432 -
Biochimica Et Biophysica Acta.... Feb 2022Cellular membranes are fundamental building blocks regulating an extensive repertoire of biological functions. These structures contain lipids and membrane proteins that... (Review)
Review
Cellular membranes are fundamental building blocks regulating an extensive repertoire of biological functions. These structures contain lipids and membrane proteins that are known to laterally self-aggregate in the plane of the membrane, forming defined membrane nanoscale domains essential for protein activity. Membrane rafts are described as heterogeneous, dynamic, and short-lived cholesterol- and sphingolipid-enriched membrane nanodomains (10-200 nm) induced by lipid-protein and lipid-lipid interactions. Those membrane nanodomains have been extensively characterized using model membranes and in silico methods. However, despite the development of advanced fluorescence microscopy techniques, undoubted nanoscale visualization by imaging techniques of membrane rafts in the membrane of unperturbed living cells is still uncompleted, increasing the skepticism about their existence. Here, we broadly review recent biochemical and microscopy techniques used to investigate membrane rafts in living cells and we enumerate persistent open questions to answer before unlocking the mystery of membrane rafts in living cells.
Topics: Cell Membrane; Humans; Ion Transport; Membrane Microdomains; Membrane Proteins; Sphingolipids
PubMed: 34748743
DOI: 10.1016/j.bbamem.2021.183813 -
Current Opinion in Lipidology Feb 2018The major cardio-protective function of HDL is to remove excess cellular cholesterol in the process of HDL particle formation and maturation. The HDL biogenic procedure... (Review)
Review
PURPOSE OF REVIEW
The major cardio-protective function of HDL is to remove excess cellular cholesterol in the process of HDL particle formation and maturation. The HDL biogenic procedure requiring protein-lipid interactions has been incompletely understood, and here we discuss recent progress and insights into the mechanism of HDL biogenesis.
RECENT FINDINGS
The initial and rate-limiting step of HDL biogenesis is the interaction between apoA-I and plasma membrane microdomains created by ATP-binding cassette transporter A1 (ABCA1) transporter. Computer simulation of molecular dynamics suggests that ABCA1 translocates phospholipids from the inner to the outer leaflet of the plasma membrane to create a transbilayer density gradient leading to the formation of an exovesiculated plasma membrane microdomain. The cryo-electron microscopy structure of ABCA1 suggests that an elongated hydrophobic tunnel formed by the extracellular domain of ABCA1 may function as a passageway to deliver lipids to apoA-I. In contrast to ABCA1-created plasma membrane microdomains, desmocollin 1 (DSC1) contained in a cholesterol-rich plasma membrane microdomain binds apoA-I to prevent HDL biogenesis. The identification of DSC1-containing plasma membrane microdomains as a negative regulator of HDL biogenesis may offer potential therapeutic avenues.
SUMMARY
Isolation and characterization of plasma membrane microdomains involved in HDL biogenesis may lead to a better understanding of the molecular mechanism of HDL biogenesis.
Topics: ATP-Binding Cassette Transporters; Animals; Cell Membrane; Gene Expression Regulation; Humans; Lipoproteins, HDL; Membrane Microdomains
PubMed: 29135688
DOI: 10.1097/MOL.0000000000000470 -
Chemistry and Physics of Lipids Nov 2020
Topics: Humans; Lipids; Membrane Microdomains; Models, Biological
PubMed: 33096095
DOI: 10.1016/j.chemphyslip.2020.105002