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BMC Biology Apr 2021Plasma membrane integrity is essential for cellular homeostasis. In vivo, cells experience plasma membrane damage from a multitude of stressors in the extra- and... (Review)
Review
Plasma membrane integrity is essential for cellular homeostasis. In vivo, cells experience plasma membrane damage from a multitude of stressors in the extra- and intra-cellular environment. To avoid lethal consequences, cells are equipped with repair pathways to restore membrane integrity. Here, we assess plasma membrane damage and repair from a whole-body perspective. We highlight the role of tissue-specific stressors in health and disease and examine membrane repair pathways across diverse cell types. Furthermore, we outline the impact of genetic and environmental factors on plasma membrane integrity and how these contribute to disease pathogenesis in different tissues.
Topics: Cell Membrane; Homeostasis
PubMed: 33849525
DOI: 10.1186/s12915-021-00972-y -
Journal of Cell Science Jul 2022The plasma membrane not only protects the cell from the extracellular environment, acting as a selective barrier, but also regulates cellular events that originate at... (Review)
Review
The plasma membrane not only protects the cell from the extracellular environment, acting as a selective barrier, but also regulates cellular events that originate at the cell surface, playing a key role in various biological processes that are essential for the preservation of cell homeostasis. Therefore, elucidation of the mechanisms involved in the maintenance of plasma membrane integrity and functionality is of utmost importance. Cells have developed mechanisms to ensure the quality of proteins that inhabit the cell surface, as well as strategies to cope with injuries inflicted to the plasma membrane. Defects in these mechanisms can lead to the development or onset of several diseases. Despite the importance of these processes, a comprehensive and holistic perspective of plasma membrane quality control is still lacking. To tackle this gap, in this Review, we provide a thorough overview of the mechanisms underlying the identification and targeting of membrane proteins that are to be removed from the cell surface, as well as the membrane repair mechanisms triggered in both physiological and pathological conditions. A better understanding of the mechanisms underlying protein quality control at the plasma membrane can reveal promising and unanticipated targets for the development of innovative therapeutic approaches.
Topics: Cell Membrane; Homeostasis; Proteins
PubMed: 35801807
DOI: 10.1242/jcs.259806 -
Neuropharmacology Jun 2020
Topics: Animals; Cell Membrane; Humans; Membrane Microdomains; Membrane Proteins; Neurons
PubMed: 32151647
DOI: 10.1016/j.neuropharm.2020.108043 -
Cells Jan 2022Golgi apparatus is the central component of the mammalian secretory pathway and it regulates the biosynthesis of the plasma membrane through three distinct but... (Review)
Review
Golgi apparatus is the central component of the mammalian secretory pathway and it regulates the biosynthesis of the plasma membrane through three distinct but interacting processes: (a) processing of protein and lipid cargoes; (b) creation of a sharp transition in membrane lipid composition by non-vesicular transport of lipids; and (c) vesicular sorting of proteins and lipids at the trans-Golgi network to target them to appropriate compartments. We discuss the molecules involved in these processes and their importance in physiology and development. We also discuss how mutations in these molecules affect plasma membrane composition and signaling leading to genetic diseases and cancer.
Topics: Animals; Cell Membrane; Golgi Apparatus; Mammals; Membrane Lipids; Protein Transport; trans-Golgi Network
PubMed: 35159178
DOI: 10.3390/cells11030368 -
Traffic (Copenhagen, Denmark) Nov 2020This review considers the following hypotheses, some well-supported and some speculative. Almost all of the sterol molecules in plasma membranes are associated with... (Review)
Review
This review considers the following hypotheses, some well-supported and some speculative. Almost all of the sterol molecules in plasma membranes are associated with bilayer phospholipids in complexes of varied strength and stoichiometry. These complexes underlie many of the material properties of the bilayer. The small fraction of cholesterol molecules exceeding the binding capacity of the phospholipids is thermodynamically active and serves diverse functions. It circulates briskly among the cell membranes, particularly through contact sites linking the organelles. Active cholesterol provides the upstream feedback signal to multiple mechanisms governing plasma membrane homeostasis, pegging the sterol level to a threshold set by its phospholipids. Active cholesterol could also be the cargo for various inter-organelle transporters and the form excreted from cells by reverse transport. Furthermore, it is integral to the function of caveolae; a mediator of Hedgehog regulation; and a ligand for the binding of cytolytic toxins to membranes. Active cholesterol modulates a variety of plasma membrane proteins-receptors, channels and transporters-at least in vitro.
Topics: Caveolae; Cell Membrane; Cholesterol; Phospholipids; Sterols
PubMed: 32930466
DOI: 10.1111/tra.12762 -
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 -
Annual Review of Biophysics May 2022Lipid-protein interactions in cells are involved in various biological processes, including metabolism, trafficking, signaling, host-pathogen interactions, and... (Review)
Review
Lipid-protein interactions in cells are involved in various biological processes, including metabolism, trafficking, signaling, host-pathogen interactions, and transmembrane transport. At the plasma membrane, lipid-protein interactions play major roles in membrane organization and function. Several membrane proteins have motifs for specific lipid binding, which modulate protein conformation and consequent function. In addition to such specific lipid-protein interactions, protein function can be regulated by the dynamic, collective behavior of lipids in membranes. Emerging analytical, biochemical, and computational technologies allow us to study the influence of specific lipid-protein interactions, as well as the collective behavior of membranes on protein function. In this article, we review the recent literature on lipid-protein interactions with a specific focus on the current state-of-the-art technologies that enable novel insights into these interactions.
Topics: Biological Phenomena; Cell Membrane; Lipids; Membrane Proteins; Protein Conformation
PubMed: 34982570
DOI: 10.1146/annurev-biophys-090721-072718 -
Biochimica Et Biophysica Acta.... Apr 2022The plasma membrane (PM) is a highly heterogenous structure intertwined with the cortical actin cytoskeleton and extracellular matrix. This complex architecture makes it... (Review)
Review
The plasma membrane (PM) is a highly heterogenous structure intertwined with the cortical actin cytoskeleton and extracellular matrix. This complex architecture makes it difficult to study the processes taking place at the PM. Model membrane systems that are simple mimics of the PM overcome this bottleneck and allow us to study the biophysical principles underlying the processes at the PM. Among them, cell-derived giant plasma membrane vesicles (GPMVs) are considered the most physiologically relevant system, retaining the compositional complexity of the PM to a large extent. GPMVs have become a key tool in membrane research in the last few years. In this review, I will provide a brief overview of this system, summarize recent applications and discuss the limitations.
Topics: Actin Cytoskeleton; Cell Membrane; Drug Carriers; Lipidomics; Membrane Proteins; Unilamellar Liposomes
PubMed: 34990591
DOI: 10.1016/j.bbamem.2021.183857 -
Current Opinion in Cell Biology Aug 2021Caveolae are abundant plasma membrane pits formed by the coordinated action of peripheral and integral membrane proteins and membrane lipids. Here, we discuss recent... (Review)
Review
Caveolae are abundant plasma membrane pits formed by the coordinated action of peripheral and integral membrane proteins and membrane lipids. Here, we discuss recent studies that are starting to provide a glimpse of how filamentous cavin proteins, membrane-embedded caveolin proteins, and specific plasma membrane lipids are brought together to make the unique caveola surface domain. Protein assembly involves multiple low-affinity interactions that are dependent on 'fuzzy' charge-dependent interactions mediated in part by disordered cavin and caveolin domains. We propose that cavins help generate a lipid domain conducive to full insertion of caveolin into the bilayer to promote caveola formation. The synergistic assembly of these dynamic protein complexes supports the formation of a metastable membrane domain that can be readily disassembled both in response to cellular stress and during endocytic trafficking. We present a mechanistic model for generation of caveolae based on these new insights.
Topics: Caveolae; Caveolin 1; Cell Membrane; Membrane Lipids; Membrane Proteins
PubMed: 33677149
DOI: 10.1016/j.ceb.2021.01.009 -
Annual Review of Physical Chemistry Apr 2021Lateral organization in the plane of the plasma membrane is an important driver of biological processes. The past dozen years have seen increasing experimental support... (Review)
Review
Lateral organization in the plane of the plasma membrane is an important driver of biological processes. The past dozen years have seen increasing experimental support for the notion that lipid organization plays an important role in modulating this heterogeneity. Various biophysical mechanisms rooted in the concept of liquid-liquid phase separation have been proposed to explain diverse experimental observations of heterogeneity in model and cell membranes with distinct but overlapping applicability. In this review, we focus on the evidence for and the consequences of the hypothesis that the plasma membrane is poised near an equilibrium miscibility critical point. Critical phenomena explain certain features of the heterogeneity observed in cells and model systems but also go beyond heterogeneity to predict other interesting phenomena, including responses to perturbations in membrane composition.
Topics: Cell Membrane; Eukaryotic Cells; Membrane Lipids; Membrane Microdomains; Membrane Proteins
PubMed: 33710910
DOI: 10.1146/annurev-physchem-090419-115951