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Frontiers in Immunology 2021T cells communicate with the environment surface receptors. Cooperation of surface receptors regulates T-cell responses to diverse stimuli. Recently, finger-like... (Review)
Review
T cells communicate with the environment surface receptors. Cooperation of surface receptors regulates T-cell responses to diverse stimuli. Recently, finger-like membrane protrusions, microvilli, have been demonstrated to play a role in the organization of receptors and, hence, T-cell activation. However, little is known about the morphogenesis of dynamic microvilli, especially in the cells of immune system. In this review, I focus on the potential role of lipids and lipid domains in morphogenesis of microvilli. Discussed is the option that clustering of sphingolipids with phosphoinositides at the plasma membrane results in dimpling (curved) domains. Such domains can attract phosphoinositide-binding proteins and stimulate actin cytoskeleton reorganization. This process triggers cortical actin opening and bundling of actin fibres to support the growing of microvilli. Critical regulators of microvilli morphogenesis in T cells are unknown. At the end, I suggest several candidates with a potential to organize proteins and lipids in these structures.
Topics: Animals; Cell Membrane; Humans; Immunomodulation; Lipid Metabolism; Membrane Microdomains; Microvilli; Morphogenesis; Phosphatidylinositols; Protein Binding; Signal Transduction; Sphingolipids; T-Lymphocytes
PubMed: 33790891
DOI: 10.3389/fimmu.2021.613591 -
Biomolecules Jul 2020Red blood cell (RBC) deformability is altered in inherited RBC disorders but the mechanism behind this is poorly understood. Here, we explored the molecular,...
Red blood cell (RBC) deformability is altered in inherited RBC disorders but the mechanism behind this is poorly understood. Here, we explored the molecular, biophysical, morphological, and functional consequences of α-spectrin mutations in a patient with hereditary elliptocytosis (pEl) almost exclusively expressing the Pro260 variant of SPTA1 and her mother (pElm), heterozygous for this mutation. At the molecular level, the pEI RBC proteome was globally preserved but spectrin density at cell edges was increased. Decreased phosphatidylserine vs. increased lysophosphatidylserine species, and enhanced lipid peroxidation, methemoglobin, and plasma acid sphingomyelinase (aSMase) activity were observed. At the biophysical level, although membrane transversal asymmetry was preserved, curvature at RBC edges and rigidity were increased. Lipid domains were altered for membrane:cytoskeleton anchorage, cholesterol content and response to Ca exchange stimulation. At the morphological and functional levels, pEl RBCs exhibited reduced size and circularity, increased fragility and impaired membrane Ca exchanges. The contribution of increased membrane curvature to the pEl phenotype was shown by mechanistic experiments in healthy RBCs upon lysophosphatidylserine membrane insertion. The role of lipid domain defects was proved by cholesterol depletion and aSMase inhibition in pEl. The data indicate that aberrant membrane content and biophysical properties alter pEl RBC morphology and functionality.
Topics: Cholesterol; Elliptocytosis, Hereditary; Erythrocyte Membrane; Erythrocytes; Humans; Lysophospholipids; Membrane Fluidity; Membrane Microdomains; Oxidative Stress
PubMed: 32751168
DOI: 10.3390/biom10081120 -
The Journal of Physical Chemistry. B Sep 2020Membrane proteins and lipids have the capacity to associate into lateral domains in cell membranes through mutual or collective interactions. Lipid rafts are functional...
Membrane proteins and lipids have the capacity to associate into lateral domains in cell membranes through mutual or collective interactions. Lipid rafts are functional lateral domains that are formed through collective interactions of certain lipids and which can include or exclude proteins. These domains have been implicated in cell signaling and protein trafficking and seem to be of importance for virus-host interactions. We therefore want to investigate if raft and viral membrane proteins present similar structural features, and how these features are distributed throughout viruses. For this purpose, we performed a bioinformatics analysis of raft and viral membrane proteins from available online databases and compared them to nonraft proteins. In general, transmembrane proteins of rafts and viruses had higher proportions of palmitoyl and phosphoryl residues compared to nonraft proteins. They differed in terms of transmembrane domain length and thickness, with viral proteins being generally shorter and having a smaller accessible surface area per residue. Nontransmembrane raft proteins had increased amounts of palmitoyl, prenyl, and phosphoryl moieties while their viral counterparts were largely myristoylated and phosphorylated. Several of these structural determinants such as phosphorylation are new to the raft field and are extensively discussed in terms of raft functionality and phase separation. Surprisingly, the proportion of palmitoylated viral transmembrane proteins was inversely correlated to the virus size which indicated the implication of palmitoylation in virus membrane curvature and possibly budding. The current results provide new insights into the raft-virus interplay and unveil possible targets for antiviral compounds.
Topics: Cell Membrane; Humans; Lipids; Lipoylation; Membrane Microdomains; Membrane Proteins; Viral Proteins
PubMed: 32813532
DOI: 10.1021/acs.jpcb.0c03435 -
Frontiers in Immunology 2021
Topics: Disease Resistance; Host-Pathogen Interactions; Humans; Immunity; Membrane Microdomains
PubMed: 33732267
DOI: 10.3389/fimmu.2021.654776 -
The Journal of Cell Biology May 2024Different membrane microdomain compositions provide unique environments that can regulate signaling receptor function. We identify microdomains on the endosome membrane...
Different membrane microdomain compositions provide unique environments that can regulate signaling receptor function. We identify microdomains on the endosome membrane of Drosophila endosomes, enriched in lipid-raft or clathrin/ESCRT-0, which are associated with Notch activation by distinct, ligand-independent mechanisms. Transfer of Notch between microdomains is regulated by Deltex and Suppressor of deltex ubiquitin ligases and is limited by a gate-keeper role for ESCRT complexes. Ubiquitination of Notch by Deltex recruits it to the clathrin/ESCRT-0 microdomain and enhances Notch activation by an ADAM10-independent/TRPML-dependent mechanism. This requirement for Deltex is bypassed by the downregulation of ESCRT-III. In contrast, while ESCRT-I depletion also activates Notch, it does so by an ADAM10-dependent/TRPML-independent mechanism and Notch is retained in the lipid raft-like microdomain. In the absence of such endosomal perturbation, different activating Notch mutations also localize to different microdomains and are activated by different mechanisms. Our findings demonstrate the interplay between Notch regulators, endosomal trafficking components, and Notch genetics, which defines membrane locations and activation mechanisms.
Topics: Animals; ADAM10 Protein; Clathrin; Down-Regulation; Drosophila; Drosophila Proteins; Endosomal Sorting Complexes Required for Transport; Endosomes; Transient Receptor Potential Channels; Receptors, Notch; Ubiquitination; Membrane Proteins; Membrane Microdomains
PubMed: 38358349
DOI: 10.1083/jcb.202211041 -
Aging Cell Aug 2023"Lipid raft aging" in nerve cells represents an early event in the development of aging-related neurodegenerative diseases, such as Alzheimer's disease. Lipid rafts are...
"Lipid raft aging" in nerve cells represents an early event in the development of aging-related neurodegenerative diseases, such as Alzheimer's disease. Lipid rafts are key elements in synaptic plasticity, and their modification with aging alters interactions and distribution of signaling molecules, such as glutamate receptors and ion channels involved in memory formation, eventually leading to cognitive decline. In the present study, we have analyzed, in vivo, the effects of dietary supplementation of n-3 LCPUFA on the lipid structure, membrane microviscosity, domain organization, and partitioning of ionotropic and metabotropic glutamate receptors in hippocampal lipid raffs in female mice. The results revealed several lipid signatures of "lipid rafts aging" in old mice fed control diets, consisting in depletion of n-3 LCPUFA, membrane unsaturation, along with increased levels of saturates, plasmalogens, and sterol esters, as well as altered lipid relevant indexes. These changes were paralleled by increased microviscosity and changes in the raft/non-raft (R/NR) distribution of AMPA-R and mGluR5. Administration of the n-3 LCPUFA diet caused the partial reversion of fatty acid alterations found in aged mice and returned membrane microviscosity to values found in young animals. Paralleling these findings, lipid rafts accumulated mGluR5, NMDA-R, and ASIC2, and increased their R/NR proportions, which collectively indicate changes in synaptic plasticity. Unexpectedly, this diet also modified the lipidome and dimension of lipid rafts, as well as the domain redistribution of glutamate receptors and acid-sensing ion channels involved in hippocampal synaptic plasticity, likely modulating functionality of lipid rafts in memory formation and reluctance to age-associated cognitive decline.
Topics: Female; Mice; Animals; Fatty Acids; Fatty Acids, Unsaturated; Hippocampus; Membrane Microdomains; Diet
PubMed: 37254617
DOI: 10.1111/acel.13867 -
Traffic (Copenhagen, Denmark) Jan 2020Many plasma membrane (PM) functions depend on the cholesterol concentration in the PM in strikingly nonlinear, cooperative ways: fully functional in the presence of... (Review)
Review
Many plasma membrane (PM) functions depend on the cholesterol concentration in the PM in strikingly nonlinear, cooperative ways: fully functional in the presence of physiological cholesterol levels (35~45 mol%), and nonfunctional below 25 mol% cholesterol; namely, still in the presence of high concentrations of cholesterol. This suggests the involvement of cholesterol-based complexes/domains formed cooperatively. In this review, by examining the results obtained by using fluorescent lipid analogs and avoiding the trap of circular logic, often found in the raft literature, we point out the fundamental similarities of liquid-ordered (Lo)-phase domains in giant unilamellar vesicles, Lo-phase-like domains formed at lower temperatures in giant PM vesicles, and detergent-resistant membranes: these domains are formed by cooperative interactions of cholesterol, saturated acyl chains, and unsaturated acyl chains, in the presence of >25 mol% cholesterol. The literature contains evidence, indicating that the domains formed by the same basic cooperative molecular interactions exist and play essential roles in signal transduction in the PM. Therefore, as a working definition, we propose that raft domains in the PM are liquid-like molecular complexes/domains formed by cooperative interactions of cholesterol with saturated acyl chains as well as unsaturated acyl chains, due to saturated acyl chains' weak multiple accommodating interactions with cholesterol and cholesterol's low miscibility with unsaturated acyl chains and TM proteins. Molecules move within raft domains and exchange with those in the bulk PM. We provide a logically established collection of fluorescent lipid probes that preferentially partition into raft and non-raft domains, as defined here, in the PM.
Topics: Cell Membrane; Cholesterol; Lipids; Membrane Microdomains; Unilamellar Liposomes
PubMed: 31760668
DOI: 10.1111/tra.12718 -
Frontiers in Immunology 2020is a Gram-positive foodborne bacterial pathogen capable of interacting and crossing the intestinal barrier, blood-brain barrier, and placental barrier to cause deadly... (Review)
Review
is a Gram-positive foodborne bacterial pathogen capable of interacting and crossing the intestinal barrier, blood-brain barrier, and placental barrier to cause deadly infection with high mortality. is an intracellular pathogen characterized by its ability to enter non-phagocytic cells. Expression of the cytolysin listeriolysin O has been shown to be the main virulence determinant and in mouse models. can also perform cell-to-cell spreading using actin-rich membrane protrusions to infect neighboring cells, which also constitutes an important strategy for infection. These events including entry into host cells, interaction between listeriolysin O and host plasma membrane, and bacterial cell-to-cell spreading have been demonstrated to implicate the cholesterol-rich lipid rafts or molecules in these microdomains in the host plasma membrane with tissue culture models. Here we review the contribution of lipid rafts on plasma membrane to infection.
Topics: Animals; Bacterial Toxins; Heat-Shock Proteins; Hemolysin Proteins; Host-Pathogen Interactions; Humans; Listeria monocytogenes; Listeriosis; Membrane Microdomains; Virulence
PubMed: 32849575
DOI: 10.3389/fimmu.2020.01666 -
International Journal of Molecular... Jan 2021Lipid rafts are critical cell membrane lipid platforms enriched in sphingolipid and cholesterol content involved in diverse cellular processes. They have been proposed... (Review)
Review
Lipid rafts are critical cell membrane lipid platforms enriched in sphingolipid and cholesterol content involved in diverse cellular processes. They have been proposed to influence membrane properties and to accommodate receptors within themselves by facilitating their interaction with ligands. Over the past decade, technical advances have improved our understanding of lipid rafts as bioactive structures. In this review, we will cover the more recent findings about cholesterol, sphingolipids and lipid rafts located in cellular and nuclear membranes in cancer. Collectively, the data provide insights on the role of lipid rafts as biomolecular targets in cancer with good perspectives for the development of innovative therapeutic strategies.
Topics: Animals; Antineoplastic Agents; Biomarkers, Tumor; Cell Membrane; Cholesterol; Humans; Membrane Microdomains; Molecular Targeted Therapy; Neoplasms; Nuclear Envelope; Sphingolipids
PubMed: 33450869
DOI: 10.3390/ijms22020726 -
Cells Sep 2021ER lipid raft-associated protein 1 (ERLIN1) and 2 (ERLIN2) are 40 kDa transmembrane glycoproteins belonging to the family of prohibitins, containing a PHB domain. They... (Review)
Review
ER lipid raft-associated protein 1 (ERLIN1) and 2 (ERLIN2) are 40 kDa transmembrane glycoproteins belonging to the family of prohibitins, containing a PHB domain. They are generally localized in the endoplasmic reticulum (ER), where ERLIN1 forms a heteroligomeric complex with its closely related ERLIN2. Well-defined functions of ERLINS are promotion of ER-associated protein degradation, mediation of inositol 1,4,5-trisphosphate (IP) receptors, processing and regulation of lipid metabolism. Until now, ERLINs have been exclusively considered protein markers of ER lipid raft-like microdomains. However, under pathophysiological conditions, they have been described within mitochondria-associated endoplasmic reticulum membranes (MAMs), tethering sites between ER and mitochondria, characterized by the presence of specialized raft-like subdomains enriched in cholesterol and gangliosides, which play a key role in the membrane scrambling and function. In this context, it is emerging that ER lipid raft-like microdomains proteins, i.e., ERLINs, may drive mitochondria-ER crosstalk under both physiological and pathological conditions by association with MAMs, regulating the two main processes underlined, survival and death. In this review, we describe the role of ERLINs in determining cell fate by controlling the "interchange" between apoptosis and autophagy pathways, considering that their alteration has a significant impact on the pathogenesis of several human diseases.
Topics: Apoptosis; Autophagy; Calcium Signaling; Endoplasmic Reticulum; Humans; Lipid Metabolism; Membrane Microdomains; Mitochondrial Membranes; Nerve Tissue Proteins; Prohibitins
PubMed: 34572057
DOI: 10.3390/cells10092408