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The Journal of Membrane Biology Oct 2022We review the current theories of nanodomain, or "raft," formation. We emphasize that the idea that they are co-exisiting Lo and Ld phases is fraught with difficulties,... (Review)
Review
We review the current theories of nanodomain, or "raft," formation. We emphasize that the idea that they are co-exisiting Lo and Ld phases is fraught with difficulties, as is the closely related idea that they are due to critical fluctuations. We then review an alternate theory that the plasma membrane is a two-dimensional microemulsion, and that the mechanism that drives to zero the line tension between Lo and Ld phases is the coupling of height and composition fluctuations. The theory yields rafts of SM and cholesterol in the outer leaf and POPS and POPC in the inner leaf. The "sea" between rafts consists of POPC in the outer leaf and POPE and cholesterol in the inner leaf. The characteristic size of the domain structures is tens of nanometers.
Topics: Membrane Microdomains; Cholesterol; Cell Membrane
PubMed: 35084528
DOI: 10.1007/s00232-021-00213-x -
Sub-cellular Biochemistry 2022Eukaryotic cells are capable of internalizing different types of cargo by plasma membrane ruffling and forming vesicles in a process known as endocytosis. The most...
Eukaryotic cells are capable of internalizing different types of cargo by plasma membrane ruffling and forming vesicles in a process known as endocytosis. The most extensively characterized endocytic pathways are clathrin-coated pits, lipid raft/caveolae-mediated endocytosis, phagocytosis, and macropinocytosis. Macropinocytosis is unique among all the endocytic processes due to its nonselective internalization of extracellular fluid, solutes, and membrane in large endocytic vesicles known as macropinosomes with unique susceptibility toward Na+/H+ exchanger inhibitors. Range of cell types capable of macropinocytosis and known to play important role in different physiological processes, which include antigen presentation, nutrient sensing, migration, and signaling. Understanding the physiological function of macropinocytosis will be helpful in filling the gaps in our knowledge and which can be exploited to develop novel therapeutic targets. In this chapter, we discuss the different molecular mechanisms that initiate the process of macropinocytosis with special emphasis on proteins involved and their diversified role in different cell types.
Topics: Endocytosis; Endosomes; Membrane Microdomains; Phagocytosis; Pinocytosis
PubMed: 35378700
DOI: 10.1007/978-3-030-94004-1_1 -
Circulation Research Feb 2016Elevated levels of cholesteryl ester (CE)-enriched apoB containing plasma lipoproteins lead to increased foam cell formation, the first step in the development of... (Review)
Review
Elevated levels of cholesteryl ester (CE)-enriched apoB containing plasma lipoproteins lead to increased foam cell formation, the first step in the development of atherosclerosis. Unregulated uptake of low-density lipoprotein cholesterol by circulating monocytes and other peripheral blood cells takes place through scavenger receptors and over time causes disruption in cellular cholesterol homeostasis. As lipoproteins are taken up, their CE core is hydrolyzed by liposomal lipases to generate free cholesterol (FC). FC can be either re-esterified and stored as CE droplets or shuttled to the plasma membrane for ATP-binding cassette transporter A1-mediated efflux. Because cholesterol is an essential component of all cellular membranes, some FC may be incorporated into microdomains or lipid rafts. These platforms are essential for receptor signaling and transduction, requiring rapid assembly and disassembly. ATP-binding cassette transporter A1 plays a major role in regulating microdomain cholesterol and is most efficient when lipid-poor apolipoprotein AI (apoAI) packages raft cholesterol into soluble particles that are eventually catabolized by the liver. If FC is not effluxed from the cell, it becomes esterified, CE droplets accumulate and microdomain cholesterol content becomes poorly regulated. This dysregulation leads to prolonged activation of immune cell signaling pathways, resulting in receptor oversensitization. The availability of apoAI or other amphipathic α-helix-rich apoproteins relieves the burden of excess microdomain cholesterol in immune cells allowing a reduction in immune cell proliferation and infiltration, thereby stimulating regression of foam cells in the artery. Therefore, cellular balance between FC and CE is essential for proper immune cell function and prevents chronic immune cell overstimulation and proliferation.
Topics: ATP Binding Cassette Transporter 1; Animals; Arteries; Atherosclerosis; Cholesterol; Cholesterol Esters; Cholesterol, HDL; Cholesterol, LDL; Esterification; Foam Cells; Humans; Hydrolysis; Inflammation; Lymphocyte Activation; Membrane Microdomains; T-Lymphocytes
PubMed: 26892966
DOI: 10.1161/CIRCRESAHA.115.306246 -
Chemistry and Physics of Lipids Jan 2015Cellular membranes define the functional geometry of intracellular space. Formation of new membrane compartments and maintenance of complex organelles require division... (Review)
Review
Cellular membranes define the functional geometry of intracellular space. Formation of new membrane compartments and maintenance of complex organelles require division and disconnection of cellular membranes, a process termed membrane fission. Peripheral membrane proteins generally control membrane remodeling during fission. Local membrane stresses, reflecting molecular geometry of membrane-interacting parts of these proteins, sum up to produce the key membrane geometries of fission: the saddle-shaped neck and hour-glass hemifission intermediate. Here, we review the fundamental principles behind the translation of molecular geometry into membrane shape and topology during fission. We emphasize the central role the membrane insertion of specialized protein domains plays in orchestrating fission in vitro and in cells. We further compare individual to synergistic action of the membrane insertion during fission mediated by individual protein species, proteins complexes or membrane domains. Finally, we describe how local geometry of fission intermediates defines the functional design of the protein complexes catalyzing fission of cellular membranes.
Topics: Cell Membrane; Membrane Microdomains; Thermodynamics
PubMed: 25062896
DOI: 10.1016/j.chemphyslip.2014.07.006 -
Microbiology Spectrum Aug 2023Many eukaryotic membrane-dependent functions are often spatially and temporally regulated by membrane microdomains (FMMs), also known as lipid rafts. These domains are...
Many eukaryotic membrane-dependent functions are often spatially and temporally regulated by membrane microdomains (FMMs), also known as lipid rafts. These domains are enriched in polyisoprenoid lipids and scaffolding proteins belonging to the tomatin, rohibitin, lotillin, and flK/C (SPFH) protein superfamily that was also identified in Gram-positive bacteria. In contrast, little is still known about FMMs in Gram-negative bacteria. In Escherichia coli K-12, 4 SPFH proteins, YqiK, QmcA, HflK, and HflC, were shown to localize in discrete polar or lateral inner membrane locations, raising the possibility that E. coli SPFH proteins could contribute to the assembly of inner membrane FMMs and the regulation of cellular processes. Here, we studied the determinant of the localization of QmcA and HflC and showed that FMM-associated cardiolipin lipid biosynthesis is required for their native localization pattern. Using Biolog phenotypic arrays, we showed that a mutant lacking all SPFH genes displayed increased sensitivity to aminoglycosides and oxidative stress that is due to the absence of HflKC. Our study therefore provides further insights into the contribution of SPFH proteins to stress tolerance in E. coli. Eukaryotic cells often segregate physiological processes in cholesterol-rich functional membrane microdomains. These domains are also called lipid rafts and contain proteins of the tomatin, rohibitin, lotillin, and flK/C (SPFH) superfamily, which are also present in prokaryotes but have been mostly studied in Gram-positive bacteria. Here, we showed that the cell localization of the SPFH proteins QmcA and HflKC in the Gram-negative bacterium E. coli is altered in the absence of cardiolipin lipid synthesis. This suggests that cardiolipins contribute to E. coli membrane microdomain assembly. Using a broad phenotypic analysis, we also showed that HflKC contribute to E. coli tolerance to aminoglycosides and oxidative stress. Our study, therefore, provides new insights into the cellular processes associated with SPFH proteins in E. coli.
Topics: Escherichia coli Proteins; Escherichia coli; Prohibitins; Aminoglycosides; Cardiolipins; Escherichia coli K12; Membrane Microdomains; Oxidative Stress; Anti-Bacterial Agents
PubMed: 37347165
DOI: 10.1128/spectrum.01767-23 -
Trends in Cell Biology Feb 2021Membrane protein organization is essential for proper cellular functioning and the result of a dynamic exchange between protein monomers, nanoscale protein clusters, and... (Review)
Review
Membrane protein organization is essential for proper cellular functioning and the result of a dynamic exchange between protein monomers, nanoscale protein clusters, and microscale higher-order structures. This exchange is affected by both lipid bilayer intrinsic factors, such as lipid rafts and tetraspanins, and extrinsic factors, such as cortical actin and galectins. Because membrane organizers act jointly like instruments in a symphony, it is challenging to define the 'key' organizers. Here, we posit, for the first time, definitions of key intrinsic and extrinsic membrane organizers. Tetraspanin nanodomains are key organizers that are often overlooked. We discuss how different key organizers can collaborate, which is important to get a full grasp of plasma membrane biology.
Topics: Cell Membrane; Humans; Membrane Microdomains; Membrane Proteins; Tetraspanins
PubMed: 33248874
DOI: 10.1016/j.tcb.2020.11.004 -
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 -
Methods in Molecular Biology (Clifton,... 2018Single-particle tracking has been used extensively to advance our understanding of the plasma membrane and the mechanisms controlling the movement of cell surface... (Review)
Review
Single-particle tracking has been used extensively to advance our understanding of the plasma membrane and the mechanisms controlling the movement of cell surface proteins. These studies provide fundamental insights into the regulation of membrane receptor activation and the assembly of signaling clusters. Here, we describe a method to label and track B cell receptor (BCR) and other cell surface proteins and how this method can be adapted to simultaneously track two molecular species or examine the movement of membrane proteins in relation to membrane microdomains. We recently used this method to study the role of the actin cytoskeleton in the regulation of B cell receptor dynamics at the cell surface.
Topics: Animals; B-Lymphocytes; Humans; Membrane Microdomains; Protein Transport; Receptors, Antigen, B-Cell; Single Molecule Imaging
PubMed: 29388108
DOI: 10.1007/978-1-4939-7474-0_13 -
Open Biology Aug 2021Primary cilia, antenna-like structures of the plasma membrane, detect various extracellular cues and transduce signals into the cell to regulate a wide range of... (Review)
Review
Primary cilia, antenna-like structures of the plasma membrane, detect various extracellular cues and transduce signals into the cell to regulate a wide range of functions. Lipid rafts, plasma membrane microdomains enriched in cholesterol, sphingolipids and specific proteins, are also signalling hubs involved in a myriad of physiological functions. Although impairment of primary cilia and lipid rafts is associated with various diseases, the relationship between primary cilia and lipid rafts is poorly understood. Here, we review a newly discovered interaction between primary cilia and lipid raft dynamics that occurs during Akt signalling in adipogenesis. We also discuss the relationship between primary cilia and lipid raft-mediated Akt signalling in cancer biology. This review provides a novel perspective on primary cilia in the regulation of lipid raft dynamics.
Topics: Adipogenesis; Animals; Cilia; Humans; Membrane Microdomains; Signal Transduction
PubMed: 34428960
DOI: 10.1098/rsob.210130 -
Frontiers in Immunology 2018Tetraspanins (Tspans) are a family of four-span transmembrane proteins, known as plasma membrane "master organizers." They form Tspan-enriched microdomains (TEMs or... (Review)
Review
Tetraspanins (Tspans) are a family of four-span transmembrane proteins, known as plasma membrane "master organizers." They form Tspan-enriched microdomains (TEMs or TERMs) through lateral association with one another and other membrane proteins. If multiple microdomains associate with each other, larger platforms can form. For infection, viruses interact with multiple cell surface components, including receptors, activating proteases, and signaling molecules. It appears that Tspans, such as CD151, CD82, CD81, CD63, CD9, Tspan9, and Tspan7, coordinate these associations by concentrating the interacting partners into Tspan platforms. In addition to mediating viral attachment and entry, these platforms may also be involved in intracellular trafficking of internalized viruses and assist in defining virus assembly and exit sites. In conclusion, Tspans play a role in viral infection at different stages of the virus replication cycle. The present review highlights recently published data on this topic, with a focus on events at the plasma membrane. In light of these findings, we propose a model for how Tspan interactions may organize cofactors for viral infection into distinct molecular platforms.
Topics: Animals; Biomarkers; Endocytosis; Host-Pathogen Interactions; Humans; Membrane Microdomains; Membrane Proteins; Structure-Activity Relationship; Tetraspanins; Virus Diseases; Virus Internalization
PubMed: 29887866
DOI: 10.3389/fimmu.2018.01140