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Cells Jun 2023Plasma membrane repair is an essential cellular mechanism that reseals membrane disruptions after a variety of insults, and compromised repair capacity can contribute to... (Review)
Review
Plasma membrane repair is an essential cellular mechanism that reseals membrane disruptions after a variety of insults, and compromised repair capacity can contribute to the progression of many diseases. Neurodegenerative diseases are marked by membrane damage from many sources, reduced membrane integrity, elevated intracellular calcium concentrations, enhanced reactive oxygen species production, mitochondrial dysfunction, and widespread neuronal death. While the toxic intracellular effects of these changes in cellular physiology have been defined, the specific mechanism of neuronal death in certain neurodegenerative diseases remains unclear. An abundance of recent evidence indicates that neuronal membrane damage and pore formation in the membrane are key contributors to neurodegenerative disease pathogenesis. In this review, we have outlined evidence supporting the hypothesis that membrane damage is a contributor to neurodegenerative diseases and that therapeutically enhancing membrane repair can potentially combat neuronal death.
Topics: Humans; Neurodegenerative Diseases; Reactive Oxygen Species; Cell Death; Cell Membrane
PubMed: 37371130
DOI: 10.3390/cells12121660 -
Comptes Rendus Biologies Dec 2021The plasma membrane is a physical boundary made of amphiphilic lipid molecules, proteins and carbohydrates extensions. Its role in mechanotransduction generates...
The plasma membrane is a physical boundary made of amphiphilic lipid molecules, proteins and carbohydrates extensions. Its role in mechanotransduction generates increasing attention in animal systems, where membrane tension is mainly induced by cortical actomyosin. In plant cells, cortical tension is of osmotic origin. Yet, because the plasma membrane in plant cells has comparable physical properties, findings from animal systems likely apply to plant cells too. Recent results suggest that this is indeed the case, with a role of membrane tension in vesicle trafficking, mechanosensitive channel opening or cytoskeleton organization in plant cells. Prospects for the plant science community are at least three fold: (i) to develop and use probes to monitor membrane tension in tissues, in parallel with other biochemical probes, with implications for protein activity and nanodomain clustering, (ii) to develop single cell approaches to decipher the mechanisms operating at the plant cell cortex at high spatio-temporal resolution, and (iii) to revisit the role of membrane composition at cell and tissue scale, by considering the physical implications of phospholipid properties and interactions in mechanotransduction.
Topics: Animals; Cell Membrane; Mechanotransduction, Cellular
PubMed: 35787608
DOI: 10.5802/crbiol.66 -
Theranostics 2023Cancer is generally considered a result of genetic mutations that cause epigenetic changes, leading to anomalous cellular behavior. Since 1970s, an increasing... (Review)
Review
Cancer is generally considered a result of genetic mutations that cause epigenetic changes, leading to anomalous cellular behavior. Since 1970s, an increasing understanding of the plasma membrane and specifically the lipid alterations in tumor cells have provided novel insights for cancer therapy. Moreover, the advances in nanotechnology offer a potential opportunity to target the tumor plasma membrane while minimizing side effects on normal cells. To further develop membrane lipid perturbing tumor therapy, the first section of this review demonstrates the association between plasma membrane physicochemical properties and tumor signaling, metastasis, and drug resistance. The second section highlights existing nanotherapeutic strategies for membrane disruption, including lipid peroxide accumulation, cholesterol regulation, membrane structure disruption, lipid raft immobilization, and energy-mediated plasma membrane perturbation. Finally, the third section evaluates the prospects and challenges of plasma membrane lipid perturbing therapy as a therapeutic strategy for cancers. The reviewed membrane lipid perturbing tumor therapy strategies are expected to bring about necessary changes in tumor therapy in the coming decades.
Topics: Humans; Neoplasms; Membrane Lipids; Cell Membrane; Membrane Microdomains; Nanotechnology
PubMed: 37215569
DOI: 10.7150/thno.82189 -
Bioorganic & Medicinal Chemistry Jun 2021Phosphoinositides are an important class of anionic, low abundance signaling lipids distributed throughout intracellular membranes. The plasma membrane contains three... (Review)
Review
Phosphoinositides are an important class of anionic, low abundance signaling lipids distributed throughout intracellular membranes. The plasma membrane contains three phosphoinositides: PI(4)P, PI(4,5)P, and PI(3,4,5)P. Of these, PI(4)P has remained the most mysterious, despite its characterization in this membrane more than a half-century ago. Fortunately, recent methodological innovations at the chemistry-biology interface have spurred a renaissance of interest in PI(4)P. Here, we describe these new toolsets and how they have revealed novel functions for the plasma membrane PI(4)P pool. We examine high-resolution structural characterization of the plasma membrane PI 4-kinase complex that produces PI(4)P, tools for modulating PI(4)P levels including isoform-selective PI 4-kinase inhibitors, and fluorescent probes for visualizing PI(4)P. Collectively, these chemical and biochemical approaches have revealed insights into how cells regulate synthesis of PI(4)P and its downstream metabolites as well as new roles for plasma membrane PI(4)P in non-vesicular lipid transport, membrane homeostasis and trafficking, and cell signaling pathways.
Topics: 1-Phosphatidylinositol 4-Kinase; Cell Membrane; Humans; Molecular Structure; Phosphatidylinositol Phosphates
PubMed: 33965837
DOI: 10.1016/j.bmc.2021.116190 -
International Journal of Molecular... May 2022Plasmodesmata (PD) are plant-specific channels connecting adjacent cells to mediate intercellular communication of molecules essential for plant development and defense.... (Review)
Review
Plasmodesmata (PD) are plant-specific channels connecting adjacent cells to mediate intercellular communication of molecules essential for plant development and defense. The typical PD are organized by the close apposition of the plasma membrane (PM), the desmotubule derived from the endoplasmic reticulum (ER), and spoke-like elements linking the two membranes. The plasmodesmal PM (PD-PM) is characterized by the formation of unique microdomains enriched with sphingolipids, sterols, and specific proteins, identified by lipidomics and proteomics. These components modulate PD to adapt to the dynamic changes of developmental processes and environmental stimuli. In this review, we focus on highlighting the functions of sphingolipid species in plasmodesmata, including membrane microdomain organization, architecture transformation, callose deposition and permeability control, and signaling regulation. We also briefly discuss the difference between sphingolipids and sterols, and we propose potential unresolved questions that are of help for further understanding the correspondence between plasmodesmal structure and function.
Topics: Cell Communication; Cell Membrane; Plasmodesmata; Sphingolipids; Sterols
PubMed: 35628487
DOI: 10.3390/ijms23105677 -
Biomolecules Oct 2018To alter and adjust the shape of the plasma membrane, cells harness various mechanisms of curvature generation. Many of these curvature generation mechanisms rely on the... (Review)
Review
To alter and adjust the shape of the plasma membrane, cells harness various mechanisms of curvature generation. Many of these curvature generation mechanisms rely on the interactions between peripheral membrane proteins, integral membrane proteins, and lipids in the bilayer membrane. Mathematical and computational modeling of membrane curvature generation has provided great insights into the physics underlying these processes. However, one of the challenges in modeling these processes is identifying the suitable constitutive relationships that describe the membrane free energy including protein distribution and curvature generation capability. Here, we review some of the commonly used continuum elastic membrane models that have been developed for this purpose and discuss their applications. Finally, we address some fundamental challenges that future theoretical methods need to overcome to push the boundaries of current model applications.
Topics: Cell Membrane; Hydrophobic and Hydrophilic Interactions; Membrane Proteins; Models, Molecular; Protein Binding
PubMed: 30360496
DOI: 10.3390/biom8040120 -
Current Biology : CB Apr 2018Cell-cell junctions are specializations of the plasma membrane responsible for physically integrating cells into tissues. We are now beginning to appreciate the diverse... (Review)
Review
Cell-cell junctions are specializations of the plasma membrane responsible for physically integrating cells into tissues. We are now beginning to appreciate the diverse impacts that mechanical forces exert upon the integrity and function of these junctions. Currently, this is best understood for cadherin-based adherens junctions in epithelia and endothelia, where cell-cell adhesion couples the contractile cytoskeletons of cells together to generate tissue-scale tension. Junctional tension participates in morphogenesis and tissue homeostasis. Changes in tension can also be detected by mechanotransduction pathways that allow cells to communicate with each other. In this review, we discuss progress in characterising the forces present at junctions in physiological conditions; the cellular mechanisms that generate intrinsic tension and detect changes in tension; and, finally, we consider how tissue integrity is maintained in the face of junctional stresses.
Topics: Adherens Junctions; Animals; Cadherins; Cell Adhesion; Cell Membrane; Cytoskeleton; Epithelium; Humans; Intercellular Junctions; Mechanotransduction, Cellular; Tensile Strength
PubMed: 29689229
DOI: 10.1016/j.cub.2018.02.003 -
The New Phytologist Aug 2017The membrane trafficking system is responsible for precise transportation and localization of proteins, lipids, and polysaccharides among single membrane-bound... (Review)
Review
The membrane trafficking system is responsible for precise transportation and localization of proteins, lipids, and polysaccharides among single membrane-bound organelles, the plasma membrane, and the extracellular space. While the exocytic trafficking pathway is considered to be a default transport pathway in many organisms, including land plants, research has shown that evolutionary processes led to an increase in the number of machinery components involved in the plant exocytic pathway. This study provides an overview of the diversification of exocytic trafficking pathways in plants, which mediate the formation and maintenance of cell polarity, interaction with symbiotic and pathogenic microbes, and cytokinesis. To fulfill these functions, distinct strategies have been employed to reroute secretory/exocytic transport during land plant evolution.
Topics: Cell Membrane; Cytokinesis; Exocytosis; Models, Biological; Plants; Protein Transport
PubMed: 28543308
DOI: 10.1111/nph.14613 -
International Journal of Molecular... Aug 2016Exosomes and ectosomes, extracellular vesicles of two types generated by all cells at multivesicular bodies and the plasma membrane, respectively, play critical roles in... (Review)
Review
Exosomes and ectosomes, extracellular vesicles of two types generated by all cells at multivesicular bodies and the plasma membrane, respectively, play critical roles in physiology and pathology. A key mechanism of their function, analogous for both types of vesicles, is the fusion of their membrane to the plasma membrane of specific target cells, followed by discharge to the cytoplasm of their luminal cargo containing proteins, RNAs, and DNA. Here we summarize the present knowledge about the interactions, binding and fusions of vesicles with the cell plasma membrane. The sequence initiates with dynamic interactions, during which vesicles roll over the plasma membrane, followed by the binding of specific membrane proteins to their cell receptors. Membrane binding is then converted rapidly into fusion by mechanisms analogous to those of retroviruses. Specifically, proteins of the extracellular vesicle membranes are structurally rearranged, and their hydrophobic sequences insert into the target cell plasma membrane which undergoes lipid reorganization, protein restructuring and membrane dimpling. Single fusions are not the only process of vesicle/cell interactions. Upon intracellular reassembly of their luminal cargoes, vesicles can be regenerated, released and fused horizontally to other target cells. Fusions of extracellular vesicles are relevant also for specific therapy processes, now intensely investigated.
Topics: Animals; Cell Membrane; Cell-Derived Microparticles; Exosomes; Humans
PubMed: 27517914
DOI: 10.3390/ijms17081296 -
Toxins Jun 2018Permeabilization of the plasma membrane represents an important threat for any cell, since it compromises its viability by disrupting cell homeostasis. Numerous... (Review)
Review
Permeabilization of the plasma membrane represents an important threat for any cell, since it compromises its viability by disrupting cell homeostasis. Numerous pathogenic bacteria produce pore-forming toxins that break plasma membrane integrity and cause cell death by colloid-osmotic lysis. Eukaryotic cells, in turn, have developed different ways to cope with the effects of such membrane piercing. Here, we provide a short overview of the general mechanisms currently proposed for plasma membrane repair, focusing more specifically on the cellular responses to membrane permeabilization by pore-forming toxins and presenting new data on the effects and cellular responses to the permeabilization by an RTX (repeats in toxin) toxin, the adenylate cyclase toxin-hemolysin secreted by the whooping cough bacterium , which we have studied in the laboratory.
Topics: Cell Membrane; Cell Membrane Permeability; Endocytosis; Eukaryotic Cells; Toxins, Biological
PubMed: 29890730
DOI: 10.3390/toxins10060234