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Cell May 2019Over the last several decades, an impressive array of advanced microscopic and analytical tools, such as single-particle tracking and nanoscopic fluorescence correlation... (Review)
Review
Over the last several decades, an impressive array of advanced microscopic and analytical tools, such as single-particle tracking and nanoscopic fluorescence correlation spectroscopy, has been applied to characterize the lateral organization and mobility of components in the plasma membrane. Such analysis can tell researchers about the local dynamic composition and structure of membranes and is important for predicting the outcome of membrane-based reactions. However, owing to the unresolved complexity of the membrane and the structures peripheral to it, identification of the detailed molecular origin of the interactions that regulate the organization and mobility of the membrane has not proceeded quickly. This Perspective presents an overview of how cell-surface structure may give rise to the types of lateral mobility that are observed and some potentially fruitful future directions to elucidate the architecture of these structures in more molecular detail.
Topics: Cell Membrane; Lipid Bilayers; Membrane Lipids; Membrane Microdomains; Membrane Proteins
PubMed: 31051105
DOI: 10.1016/j.cell.2019.04.018 -
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 -
Current Topics in Membranes 2015The lipid bilayer of the plasma membrane is thought to be compartmentalized by the presence of lipid-protein microdomains. In eukaryotic cells, microdomains composed of... (Review)
Review
The lipid bilayer of the plasma membrane is thought to be compartmentalized by the presence of lipid-protein microdomains. In eukaryotic cells, microdomains composed of sterols and sphingolipids, commonly known as lipid rafts, are believed to exist, and reports on the presence of sterol- or protein-mediated microdomains in bacterial cell membranes are also appearing. Despite increasing attention, little is known about microdomains in the plasma membrane of pathogenic microorganisms. This review attempts to provide an overview of the current state of knowledge of lipid rafts in pathogenic fungi and bacteria. The current literature on characterization of microdomains in pathogens is reviewed, and their potential role in growth, pathogenesis, and drug resistance is discussed. Better insight into the structure and function of membrane microdomains in pathogenic microorganisms might lead to a better understanding of their pathogenesis and development of raft-mediated approaches for therapy.
Topics: Animals; Bacteria; Bacterial Infections; Cholesterol; Drug Resistance; Fungi; Humans; Lipid Bilayers; Membrane Microdomains; Mycoses
PubMed: 26015285
DOI: 10.1016/bs.ctm.2015.03.005 -
Journal of Lipid Research May 2020Lipid rafts are organized plasma membrane microdomains, which provide a distinct level of regulation of cellular metabolism and response to extracellular stimuli,...
Lipid rafts are organized plasma membrane microdomains, which provide a distinct level of regulation of cellular metabolism and response to extracellular stimuli, affecting a diverse range of physiologic and pathologic processes. This Thematic Review Series focuses on Biology of Lipid Rafts rather than on their composition or structure. The aim is to provide an overview of ideas on how lipid rafts are involved in regulation of different pathways and how they interact with other layers of metabolic regulation. Articles in the series will review the involvement of lipid rafts in regulation of hematopoiesis, production of extracellular vesicles, host interaction with infection, and the development and progression of cancer, neuroinflammation, and neurodegeneration, as well as the current outlook on therapeutic targeting of lipid rafts.
Topics: Humans; Membrane Microdomains
PubMed: 31462515
DOI: 10.1194/jlr.IN119000330 -
International Journal of Molecular... Aug 2021Tetraspanins are a family of transmembrane proteins that form a network of protein-protein interactions within the plasma membrane. Within this network, tetraspanin are...
Tetraspanins are a family of transmembrane proteins that form a network of protein-protein interactions within the plasma membrane. Within this network, tetraspanin are thought to control the lateral segregation of their partners at the plasma membrane through mechanisms involving specific lipids. Here, we used a single molecule tracking approach to study the membrane behavior of tetraspanins in mammary epithelial cells and demonstrate that despite a common overall behavior, each tetraspanin (CD9, CD81 and CD82) has a specific signature in terms of dynamics. Furthermore, we demonstrated that tetraspanin dynamics on the cell surface are dependent on gangliosides. More specifically, we found that CD82 expression increases the dynamics of CD81 and alters its localization at the plasma membrane, this has no effect on the behavior of CD9. Our results provide new information on the ability of CD82 and gangliosides to differentially modulate the dynamics and organization of tetraspanins at the plasma membrane and highlight that its lipid and protein composition is involved in the dynamical architecture of the tetraspanin web. We predict that CD82 may act as a regulator of the lateral segregation of specific tetraspanins at the plasma membrane while gangliosides could play a crucial role in establishing tetraspanin-enriched areas.
Topics: Cell Membrane; Cells, Cultured; Epithelial Cells; Gangliosides; Humans; Kangai-1 Protein; Membrane Microdomains; Tetraspanin 28
PubMed: 34445169
DOI: 10.3390/ijms22168459 -
Viruses Jul 2020Retroviruses selectively incorporate a specific subset of host cell proteins and lipids into their outer membrane when they bud out from the host plasma membrane. This... (Review)
Review
Retroviruses selectively incorporate a specific subset of host cell proteins and lipids into their outer membrane when they bud out from the host plasma membrane. This specialized viral membrane composition is critical for both viral survivability and infectivity. Here, we review recent findings from live cell imaging of single virus assembly demonstrating that proteins and lipids sort into the HIV retroviral membrane by a mechanism of lipid-based phase partitioning. The findings showed that multimerizing HIV Gag at the assembly site creates a liquid-ordered lipid phase enriched in cholesterol and sphingolipids. Proteins with affinity for this specialized lipid environment partition into it, resulting in the selective incorporation of proteins into the nascent viral membrane. Building on this and other work in the field, we propose a model describing how HIV Gag induces phase separation of the viral assembly site through a mechanism involving transbilayer coupling of lipid acyl chains and membrane curvature changes. Similar phase-partitioning pathways in response to multimerizing structural proteins likely help sort proteins into the membranes of other budding structures within cells.
Topics: HIV-1; Host Microbial Interactions; Humans; Lipids; Membrane Microdomains; Protein Binding; Viral Matrix Proteins; Virus Assembly; gag Gene Products, Human Immunodeficiency Virus
PubMed: 32664429
DOI: 10.3390/v12070745 -
Cell Biology and Toxicology Oct 2017Infectious diseases pose major socioeconomic and health-related threats to millions of people across the globe. Strategies to combat infectious diseases derive from our... (Review)
Review
Infectious diseases pose major socioeconomic and health-related threats to millions of people across the globe. Strategies to combat infectious diseases derive from our understanding of the complex interactions between the host and specific bacterial, viral, and fungal pathogens. Lipid rafts are membrane microdomains that play important role in life cycle of microbes. Interaction of microbial pathogens with host membrane rafts influences not only their initial colonization but also their spread and the induction of inflammation. Therefore, intervention strategies aimed at modulating the assembly of membrane rafts and/or regulating raft-directed signaling pathways are attractive approaches for the. management of infectious diseases. The current review discusses the latest advances in terms of techniques used to study the role of membrane microdomains in various pathological conditions and provides updated information regarding the role of membrane rafts during bacterial, viral and fungal infections.
Topics: Animals; Bacterial Infections; Communicable Diseases; Humans; Membrane Microdomains; Signal Transduction; Virus Diseases
PubMed: 28275881
DOI: 10.1007/s10565-017-9386-9 -
Current Topics in Membranes 2016Palmitoylation is an evolutionally conserved lipid modification of proteins. Dynamic and reversible palmitoylation controls a wide range of molecular and cellular... (Review)
Review
Palmitoylation is an evolutionally conserved lipid modification of proteins. Dynamic and reversible palmitoylation controls a wide range of molecular and cellular properties of proteins including the protein trafficking, protein function, protein stability, and specialized membrane domain organization. However, technical difficulties in (1) detection of palmitoylated substrate proteins and (2) purification and enzymology of palmitoylating enzymes have prevented the progress in palmitoylation research, compared with that in phosphorylation research. The recent development of proteomic and chemical biology techniques has unexpectedly expanded the known complement of palmitoylated proteins in various species and tissues/cells, and revealed the unique occurrence of palmitoylated proteins in membrane-bound organelles and specific membrane compartments. Furthermore, identification and characterization of DHHC (Asp-His-His-Cys) palmitoylating enzyme-substrate pairs have contributed to elucidating the regulatory mechanisms and pathophysiological significance of protein palmitoylation. Here, we review the recent progress in protein palmitoylation at the molecular, cellular, and in vivo level and discuss how locally regulated palmitoylation machinery works for dynamic nanoscale organization of membrane domains.
Topics: Animals; Humans; Intracellular Space; Lipoylation; Membrane Microdomains; Proteins
PubMed: 26781831
DOI: 10.1016/bs.ctm.2015.10.003 -
Neuropharmacology Jun 2020
Topics: Animals; Cell Membrane; Humans; Membrane Microdomains; Membrane Proteins; Neurons
PubMed: 32151647
DOI: 10.1016/j.neuropharm.2020.108043 -
FEBS Open Bio Sep 2023Gangliosides are functional components of membrane lipid rafts that control critical functions in cell communication. Many pathologies involve raft gangliosides, which... (Review)
Review
Gangliosides are functional components of membrane lipid rafts that control critical functions in cell communication. Many pathologies involve raft gangliosides, which therefore represent an approach of choice for developing innovative therapeutic strategies. Beginning with a discussion of what a disease is (and is not), this review lists the major human pathologies that involve gangliosides, which includes cancer, diabetes, and infectious and neurodegenerative diseases. In most cases, the problem is due to a protein whose binding to gangliosides either creates a pathological condition or impairs a physiological function. Then, I draw up an inventory of the different molecular mechanisms of protein-ganglioside interactions. I propose to classify the ganglioside-binding domains of proteins into four categories, which I name GBD-1, GBD-2, GBD-3, and GBD-4. This structural and functional classification could help to rationalize the design of innovative molecules capable of disrupting the binding of selected proteins to gangliosides without generating undesirable effects. The biochemical specificities of gangliosides expressed in the human brain must also be taken into account to improve the reliability of animal models (or any animal-free alternative) of Alzheimer's and Parkinson's diseases.
Topics: Humans; Gangliosides; Reproducibility of Results; Parkinson Disease; Brain; Membrane Microdomains
PubMed: 37052878
DOI: 10.1002/2211-5463.13612