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Plant Physiology Nov 2023Cell polarity results from the asymmetric distribution of cellular structures, molecules, and functions. Polarity is a fundamental cellular trait that can determine the... (Review)
Review
Cell polarity results from the asymmetric distribution of cellular structures, molecules, and functions. Polarity is a fundamental cellular trait that can determine the orientation of cell division, the formation of particular cell shapes, and ultimately the development of a multicellular body. To maintain the distinct asymmetric distribution of proteins and lipids in cellular membranes, plant cells have developed complex trafficking and regulatory mechanisms. Major advances have been made in our understanding of how membrane microdomains influence the asymmetric distribution of proteins and lipids. In this review, we first give an overview of cell polarity. Next, we discuss current knowledge concerning membrane microdomains and their roles as structural and signaling platforms to establish and maintain membrane polarity, with a special focus on the asymmetric distribution of proteins and lipids, and advanced microscopy techniques to observe and characterize membrane microdomains. Finally, we review recent advances regarding membrane trafficking in cell polarity establishment and how the balance between exocytosis and endocytosis affects membrane polarity.
Topics: Cell Polarity; Cell Membrane; Signal Transduction; Membrane Microdomains; Lipids
PubMed: 37549378
DOI: 10.1093/plphys/kiad444 -
Traffic (Copenhagen, Denmark) Nov 2017Protein S-acylation, also known as palmitoylation, consists of the addition of a lipid molecule to one or more cysteine residues through a thioester bond. This... (Review)
Review
Protein S-acylation, also known as palmitoylation, consists of the addition of a lipid molecule to one or more cysteine residues through a thioester bond. This modification, which is widespread in eukaryotes, is thought to affect over 12% of the human proteome. S-acylation allows the reversible association of peripheral proteins with membranes or, in the case of integral membrane proteins, modulates their behavior within the plane of the membrane. This review focuses on the consequences of protein S-acylation on intracellular trafficking and membrane association. We summarize relevant information that illustrates how lipid modification of proteins plays an important role in dictating precise intracellular movements within cells by regulating membrane-cytosol exchange, through membrane microdomain segregation, or by modifying the flux of the proteins by means of vesicular or diffusional transport systems. Finally, we highlight some of the key open questions and major challenges in the field.
Topics: Acylation; Cysteine; Humans; Lipid Metabolism; Lipoylation; Membrane Microdomains; Membrane Proteins; Palmitates; Protein Transport
PubMed: 28837239
DOI: 10.1111/tra.12510 -
Nature Chemical Biology Jun 2023Plasma membrane heterogeneity has been tied to a litany of cellular functions and is often explained by analogy to membrane phase separation; however, models based on...
Plasma membrane heterogeneity has been tied to a litany of cellular functions and is often explained by analogy to membrane phase separation; however, models based on phase separation alone fall short of describing the rich organization available within cell membranes. Here we present comprehensive experimental evidence motivating an updated model of plasma membrane heterogeneity in which membrane domains assemble in response to protein scaffolds. Quantitative super-resolution nanoscopy measurements in live B lymphocytes detect membrane domains that emerge upon clustering B cell receptors (BCRs). These domains enrich and retain membrane proteins based on their preference for the liquid-ordered phase. Unlike phase-separated membranes that consist of binary phases with defined compositions, membrane composition at BCR clusters is modulated through the protein constituents in clusters and the composition of the membrane overall. This tunable domain structure is detected through the variable sorting of membrane probes and impacts the magnitude of BCR activation.
Topics: Cell Membrane; Membrane Proteins; Membrane Microdomains
PubMed: 36997644
DOI: 10.1038/s41589-023-01268-8 -
Cardiovascular Diabetology Dec 2017Cardiovascular disease, predominantly ischemic heart disease (IHD), is the leading cause of death in diabetes mellitus (DM). In addition to eliciting cardiomyopathy, DM... (Review)
Review
Cardiovascular disease, predominantly ischemic heart disease (IHD), is the leading cause of death in diabetes mellitus (DM). In addition to eliciting cardiomyopathy, DM induces a 'wicked triumvirate': (i) increasing the risk and incidence of IHD and myocardial ischemia; (ii) decreasing myocardial tolerance to ischemia-reperfusion (I-R) injury; and (iii) inhibiting or eliminating responses to cardioprotective stimuli. Changes in ischemic tolerance and cardioprotective signaling may contribute to substantially higher mortality and morbidity following ischemic insult in DM patients. Among the diverse mechanisms implicated in diabetic impairment of ischemic tolerance and cardioprotection, changes in sarcolemmal makeup may play an overarching role and are considered in detail in the current review. Observations predominantly in animal models reveal DM-dependent changes in membrane lipid composition (cholesterol and triglyceride accumulation, fatty acid saturation vs. reduced desaturation, phospholipid remodeling) that contribute to modulation of caveolar domains, gap junctions and T-tubules. These modifications influence sarcolemmal biophysical properties, receptor and phospholipid signaling, ion channel and transporter functions, contributing to contractile and electrophysiological dysfunction, cardiomyopathy, ischemic intolerance and suppression of protective signaling. A better understanding of these sarcolemmal abnormalities in types I and II DM (T1DM, T2DM) can inform approaches to limiting cardiomyopathy, associated IHD and their consequences. Key knowledge gaps include details of sarcolemmal changes in models of T2DM, temporal patterns of lipid, microdomain and T-tubule changes during disease development, and the precise impacts of these diverse sarcolemmal modifications. Importantly, exercise, dietary, pharmacological and gene approaches have potential for improving sarcolemmal makeup, and thus myocyte function and stress-resistance in this ubiquitous metabolic disorder.
Topics: Animals; Anticholesteremic Agents; Diabetes Mellitus, Type 1; Diabetes Mellitus, Type 2; Diabetic Cardiomyopathies; Diet; Disease Models, Animal; Energy Metabolism; Exercise; Humans; Hypoglycemic Agents; Membrane Lipids; Membrane Microdomains; Myocardial Infarction; Myocardial Reperfusion Injury; Myocytes, Cardiac; Prognosis; Protective Factors; Risk Factors; Sarcolemma; Signal Transduction
PubMed: 29202762
DOI: 10.1186/s12933-017-0638-z -
Journal of Lipid Research May 2020Lipid rafts regulate the initiation of cellular metabolic and signaling pathways by organizing the pathway components in ordered microdomains on the cell surface.... (Review)
Review
Lipid rafts regulate the initiation of cellular metabolic and signaling pathways by organizing the pathway components in ordered microdomains on the cell surface. Cellular responses regulated by lipid rafts range from physiological to pathological, and the success of a therapeutic approach targeting "pathological" lipid rafts depends on the ability of a remedial agent to recognize them and disrupt pathological lipid rafts without affecting normal raft-dependent cellular functions. In this article, concluding the Thematic Review Series on Biology of Lipid Rafts, we review current experimental therapies targeting pathological lipid rafts, including examples of inflammarafts and clusters of apoptotic signaling molecule-enriched rafts. The corrective approaches include regulation of cholesterol and sphingolipid metabolism and membrane trafficking by using HDL and its mimetics, LXR agonists, ABCA1 overexpression, and cyclodextrins, as well as a more targeted intervention with apoA-I binding protein. Among others, we highlight the design of antagonists that target inflammatory receptors only in their activated form of homo- or heterodimers, when receptor dimerization occurs in pathological lipid rafts. Other therapies aim to promote raft-dependent physiological functions, such as augmenting caveolae-dependent tissue repair. The overview of this highly dynamic field will provide readers with a view on the emerging concept of targeting lipid rafts as a therapeutic strategy.jlr;61/5/687/F1F1f1.
Topics: Animals; Humans; Membrane Microdomains; Molecular Targeted Therapy
PubMed: 32205411
DOI: 10.1194/jlr.TR120000658 -
Journal of Molecular Biology Dec 2016Many cell-membrane-associated processes require transient spatiotemporal separation of components on scales ranging from a couple of molecules to micrometers in size.... (Review)
Review
Many cell-membrane-associated processes require transient spatiotemporal separation of components on scales ranging from a couple of molecules to micrometers in size. Understanding these processes mechanistically involves understanding how lipids and proteins self-organize and interact with the cell cortex. Here, we review recent advances in dissecting the mechanisms of cell membrane compartmentalization. We introduce the challenges in studying cell membrane organization, the current understanding of how complex membranes self-organize to form transient domains, and the role of protein scaffolds in membrane organization. We discuss the formation of signaling domains as an important example of transient membrane compartmentalization. We conclude by pointing to the current limitations of measuring membrane organization in living cells and the steps that are required to advance the field.
Topics: Cell Membrane; Membrane Lipids; Membrane Microdomains; Membrane Proteins; Models, Biological
PubMed: 27720722
DOI: 10.1016/j.jmb.2016.09.022 -
Cellular Microbiology Dec 2021Lipid microdomains or lipid rafts are dynamic and tightly ordered regions of the plasma membrane. In mammalian cells, they are enriched in cholesterol,... (Review)
Review
Lipid microdomains or lipid rafts are dynamic and tightly ordered regions of the plasma membrane. In mammalian cells, they are enriched in cholesterol, glycosphingolipids, Glycosylphosphatidylinositol-anchored and signalling-related proteins. Several studies have suggested that mammalian pattern recognition receptors are concentrated or recruited to lipid domains during host-pathogen association to enhance the effectiveness of host effector processes. However, pathogens have also evolved strategies to exploit these domains to invade cells and survive. In fungal organisms, a complex cell wall network usually mediates the first contact with the host cells. This cell wall may contain virulence factors that interfere with the host membrane microdomains dynamics, potentially impacting the infection outcome. Indeed, the microdomain disruption can dampen fungus-host cell adhesion, phagocytosis and cellular immune responses. Here, we provide an overview of regulatory strategies employed by pathogenic fungi to engage with and potentially subvert the lipid microdomains of host cells. TAKE AWAY: Lipid microdomains are ordered regions of the plasma membrane enriched in cholesterol, glycosphingolipids (GSL), GPI-anchored and signalling-related proteins. Pathogen recognition by host immune cells can involve lipid microdomain participation. During this process, these domains can coalesce in larger complexes recruiting receptors and signalling proteins, significantly increasing their signalling abilities. The antifungal innate immune response is mediated by the engagement of pathogen-associated molecular patterns to pattern recognition receptors (PRRs) at the plasma membrane of innate immune cells. Lipid microdomains can concentrate or recruit PRRs during host cell-fungi association through a multi-interactive mechanism. This association can enhance the effectiveness of host effector processes. However, virulence factors at the fungal cell surface and extracellular vesicles can re-assembly these domains, compromising the downstream signalling and favouring the disease development. Lipid microdomains are therefore very attractive targets for novel drugs to combat fungal infections.
Topics: Animals; Cell Membrane; Glycosphingolipids; Membrane Microdomains; Mycoses; Phagocytosis; Receptors, Pattern Recognition
PubMed: 34392593
DOI: 10.1111/cmi.13385 -
Journal of Physics. Condensed Matter :... Aug 2015The architecture of biological membranes is tightly coupled to the localization, organization, and function of membrane proteins. The organelle-specific distribution of... (Review)
Review
The architecture of biological membranes is tightly coupled to the localization, organization, and function of membrane proteins. The organelle-specific distribution of lipids allows for the formation of functional microdomains (also called rafts) that facilitate the segregation and aggregation of membrane proteins and thus shape their function. Molecular dynamics simulations enable to directly access the formation, structure, and dynamics of membrane microdomains at the molecular scale and the specific interactions among lipids and proteins on timescales from picoseconds to microseconds. This review focuses on the latest developments of biomembrane force fields for both atomistic and coarse-grained molecular dynamics (MD) simulations, and the different levels of coarsening of biomolecular structures. It also briefly introduces scale-bridging methods applicable to biomembrane studies, and highlights selected recent applications.
Topics: Animals; Cell Membrane; Humans; Lipid Bilayers; Membrane Microdomains; Molecular Dynamics Simulation; Thermodynamics
PubMed: 26194872
DOI: 10.1088/0953-8984/27/32/323103 -
Current Opinion in Cell Biology Aug 2020It is widely recognized that after endocytosis, internalized cargo is delivered to endosomes that act as sorting stations. The limiting membrane of endosomes contain... (Review)
Review
It is widely recognized that after endocytosis, internalized cargo is delivered to endosomes that act as sorting stations. The limiting membrane of endosomes contain specialized subregions, or microdomains, that represent distinct functions of the endosome, including regions competing for cargo capture leading to degradation or recycling. Great progress has been made in defining the endosomal protein coats that sort cargo in these domains, including Retromer that recycles transmembrane cargo, and ESCRT (endosomal sorting complex required for transport) that degrades transmembrane cargo. In this review, we discuss recent work that is beginning to unravel how such coat complexes contribute to the creation and maintenance of endosomal microdomains. We highlight data that indicates that adjacent microdomains do not act independently but rather interact to cross-regulate. We posit that these interactions provide an agile means for the cell to adjust sorting in response to extracellular signals and intracellular metabolic cues.
Topics: Actins; Animals; Endosomes; Humans; Membrane Microdomains; Membrane Proteins; Protein Transport; Ubiquitination
PubMed: 32247230
DOI: 10.1016/j.ceb.2020.02.018 -
Biochimica Et Biophysica Acta Jul 2016Cardiac transverse tubules (t-tubules) are specific membrane organelles critical in calcium signaling and excitation-contraction coupling required for beat-to-beat heart... (Review)
Review
Cardiac transverse tubules (t-tubules) are specific membrane organelles critical in calcium signaling and excitation-contraction coupling required for beat-to-beat heart contraction. T-tubules are highly branched and form an interconnected network that penetrates the myocyte interior to form junctions with the sarcoplasmic reticulum. T-tubules are selectively enriched with specific ion channels and proteins crucial in calcium transient development necessary in excitation-contraction coupling, thus t-tubules are a key component of cardiac myocyte function. In this review, we focus primarily on two proteins concentrated within the t-tubular network, the L-type calcium channel (LTCC) and associated membrane anchor protein, bridging integrator 1 (BIN1). Here, we provide an overview of current knowledge in t-tubule morphology, composition, microdomains, as well as the dynamics of the t-tubule network. Secondly, we highlight multiple aspects of BIN1-dependent t-tubule function, which includes forward trafficking of LTCCs to t-tubules, LTCC clustering at t-tubule surface, microdomain organization and regulation at t-tubule membrane, and the formation of a slow diffusion barrier within t-tubules. Lastly, we describe progress in characterizing how acquired human heart failure can be attributed to abnormal BIN1 transcription and associated t-tubule remodeling. Understanding BIN1-regulated cardiac t-tubule biology in human heart failure management has the dual benefit of promoting progress in both biomarker development and therapeutic target identification. This article is part of a Special Issue entitled: Cardiomyocyte Biology: Integration of Developmental and Environmental Cues in the Heart edited by Marcus Schaub and Hughes Abriel.
Topics: Adaptor Proteins, Signal Transducing; Animals; Calcium Channels, L-Type; Calcium Signaling; Genetic Predisposition to Disease; Heart Failure; Humans; Membrane Microdomains; Membrane Potentials; Myocytes, Cardiac; Nuclear Proteins; Protein Binding; Protein Transport; Risk Factors; Sarcolemma; Transcription, Genetic; Tumor Suppressor Proteins
PubMed: 26578114
DOI: 10.1016/j.bbamcr.2015.11.004