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Molecules (Basel, Switzerland) Dec 2023Lipid membrane nanodomains or lipid rafts are 10-200 nm diameter size cholesterol- and sphingolipid-enriched domains of the plasma membrane, gathering many proteins with... (Review)
Review
Lipid membrane nanodomains or lipid rafts are 10-200 nm diameter size cholesterol- and sphingolipid-enriched domains of the plasma membrane, gathering many proteins with different roles. Isolation and characterization of plasma membrane proteins by differential centrifugation and proteomic studies have revealed a remarkable diversity of proteins in these domains. The limited size of the lipid membrane nanodomain challenges the simple possibility that all of them can coexist within the same lipid membrane domain. As caveolin-1, flotillin isoforms and gangliosides are currently used as neuronal lipid membrane nanodomain markers, we first analyzed the structural features of these components forming nanodomains at the plasma membrane since they are relevant for building supramolecular complexes constituted by these molecular signatures. Among the proteins associated with neuronal lipid membrane nanodomains, there are a large number of proteins that play major roles in calcium signaling, such as ionotropic and metabotropic receptors for neurotransmitters, calcium channels, and calcium pumps. This review highlights a large variation between the calcium signaling proteins that have been reported to be associated with isolated caveolin-1 and flotillin-lipid membrane nanodomains. Since these calcium signaling proteins are scattered in different locations of the neuronal plasma membrane, i.e., in presynapses, postsynapses, axonal or dendritic trees, or in the neuronal soma, our analysis suggests that different lipid membrane-domain subtypes should exist in neurons. Furthermore, we conclude that classification of lipid membrane domains by their content in calcium signaling proteins sheds light on the roles of these domains for neuronal activities that are dependent upon the intracellular calcium concentration. Some examples described in this review include the synaptic and metabolic activity, secretion of neurotransmitters and neuromodulators, neuronal excitability (long-term potentiation and long-term depression), axonal and dendritic growth but also neuronal cell survival and death.
Topics: Caveolin 1; Calcium Signaling; Calcium; Proteomics; Membrane Microdomains; Neurons; Gangliosides; Neurotransmitter Agents
PubMed: 38067638
DOI: 10.3390/molecules28237909 -
Communications Biology Apr 2020Cystic Fibrosis (CF) is the most common life-shortening genetic disease among Caucasians, resulting from mutations in the gene encoding the Cystic Fibrosis Transmembrane... (Review)
Review
Cystic Fibrosis (CF) is the most common life-shortening genetic disease among Caucasians, resulting from mutations in the gene encoding the Cystic Fibrosis Transmembrane conductance Regulator (CFTR). While work to understand this protein has resulted in new treatment strategies, it is important to emphasize that CFTR exists within a complex lipid bilayer - a concept largely overlooked when performing structural and functional studies. In this review we discuss cellular lipid imbalances in CF, mechanisms by which lipids affect membrane protein activity, and the specific impact of detergents and lipids on CFTR function.
Topics: Aminophenols; Aminopyridines; Animals; Benzodioxoles; Cystic Fibrosis; Cystic Fibrosis Transmembrane Conductance Regulator; Drug Combinations; Epithelial Cells; Humans; Lung; Membrane Lipids; Membrane Microdomains; Mutation; Protein Conformation; Protein Stability; Protein Transport; Quinolones; Structure-Activity Relationship
PubMed: 32313074
DOI: 10.1038/s42003-020-0909-1 -
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 -
Chembiochem : a European Journal of... Jul 2023Glycosphingolipid (GSL) and glycosylphosphatidylinositol (GPI) are the two major glycolipids expressed by eukaryotic cells, and their metabolisms share the same... (Review)
Review
Glycosphingolipid (GSL) and glycosylphosphatidylinositol (GPI) are the two major glycolipids expressed by eukaryotic cells, and their metabolisms share the same machineries. Moreover, both GSLs and GPI-anchored proteins (GPI-APs) are localized in the cholesterol-rich regions, namely the lipid rafts, of the cell membrane, where many other signaling molecules are compartmentalized as well. Therefore, the interaction between GSLs and GPI-APs and their interactions with other molecules in the lipid rafts are inevitable. This review is focused on the influences of GSLs and GPI-APs on each other's biosynthesis, trafficking, cell membrane distribution, and biological functions, such as signal transduction.
Topics: Glycosphingolipids; Glycosylphosphatidylinositols; Cell Membrane; Proteins; Membrane Microdomains
PubMed: 36935354
DOI: 10.1002/cbic.202200761 -
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 -
Current Biology : CB Dec 2021Jonathan Waters provides an introduction to seaweed rafts and their role in the dispersal of marine and coastal species.
Jonathan Waters provides an introduction to seaweed rafts and their role in the dispersal of marine and coastal species.
Topics: Membrane Microdomains; Seaweed
PubMed: 34875235
DOI: 10.1016/j.cub.2021.10.053 -
Cancer Metastasis Reviews Jun 2020Several studies have demonstrated interactions between the two leaflets in membrane bilayers and the importance of specific lipid species for such interaction and... (Review)
Review
Several studies have demonstrated interactions between the two leaflets in membrane bilayers and the importance of specific lipid species for such interaction and membrane function. We here discuss these investigations with a focus on the sphingolipid and cholesterol-rich lipid membrane domains called lipid rafts, including the small flask-shaped invaginations called caveolae, and the importance of such membrane structures in cell biology and cancer. We discuss the possible interactions between the very long-chain sphingolipids in the outer leaflet of the plasma membrane and the phosphatidylserine species PS 18:0/18:1 in the inner leaflet and the importance of cholesterol for such interactions. We challenge the view that lipid rafts contain a large fraction of lipids with two saturated fatty acyl groups and argue that it is important in future studies of membrane models to use asymmetric membrane bilayers with lipid species commonly found in cellular membranes. We also discuss the need for more quantitative lipidomic studies in order to understand membrane function and structure in general, and the importance of lipid rafts in biological systems. Finally, we discuss cancer-related changes in lipid rafts and lipid composition, with a special focus on changes in glycosphingolipids and the possibility of using lipid therapy for cancer treatment.
Topics: Animals; Cell Membrane; Cholesterol; Glycosphingolipids; Humans; Lipid Bilayers; Lipid Metabolism; Membrane Microdomains; Neoplasms; Phosphatidylserines; Sphingolipids
PubMed: 32314087
DOI: 10.1007/s10555-020-09872-z -
Frontiers in Cell and Developmental... 2020Membrane microdomains, also called lipid rafts, are areas on membrane enriched in glycolipids, sphingolipids, and cholesterol. Although membrane microdomains are thought... (Review)
Review
Membrane microdomains, also called lipid rafts, are areas on membrane enriched in glycolipids, sphingolipids, and cholesterol. Although membrane microdomains are thought to play key roles in many cellular functions, their structures, properties, and biological functions remain obscure. Cellular membranes contain several types of glycoproteins, glycolipids, and other lipids, including cholesterol, glycerophospholipids, and sphingomyelin. Depending on their physicochemical properties, especially the characteristics of their glycolipids, various microdomains form on these cell membranes, providing structural or functional contextures thought to be essential for biological activities. For example, the plasma membranes of human neutrophils are enriched in lactosylceramide (LacCer) and phosphatidylglucoside (PtdGlc), each of which forms different membrane microdomains with different surrounding molecules and is involved in different functions of neutrophils. Specifically, LacCer forms Lyn-coupled lipid microdomains, which mediate neutrophil chemotaxis, phagocytosis, and superoxide generation, whereas PtdGlc-enriched microdomains mediate neutrophil differentiation and spontaneous apoptosis. However, the mechanisms by which these glycolipids form different nano/meso microdomains and mediate their specialized functions remain incompletely understood. This review describes current understanding of the roles of glycolipids and sphingolipids in their enriched contextures on cellular membranes, including their mechanisms of facilitation and regulation of intracellular signaling. This review also introduces new concepts about the roles of glycolipid and sphingolipid-dependent contextures in immunological functions.
PubMed: 33195253
DOI: 10.3389/fcell.2020.589799