Review

Authors: Doralicia Casares, Pablo V Escribá, Catalina Ana Rosselló...

Biological membranes are key elements for the maintenance of cell architecture and physiology. Beyond a pure barrier separating the inner space of the cell from the outer, the plasma membrane is a scaffold and player in cell-to-cell communication and the initiation of intracellular signals among other functions. Critical to this function is the plasma membrane compartmentalization in lipid microdomains that control the localization and productive interactions of proteins involved in cell signal propagation. In addition, cells are divided into compartments limited by other membranes whose integrity and homeostasis are finely controlled, and which determine the identity and function of the different organelles. Here, we review current knowledge on membrane lipid composition in the plasma membrane and endomembrane compartments, emphasizing its role in sustaining organelle structure and function. The correct composition and structure of cell membranes define key pathophysiological aspects of cells. Therefore, we explore the therapeutic potential of manipulating membrane lipid composition with approaches like membrane lipid therapy, aiming to normalize cell functions through the modification of membrane lipid bilayers.

Topics: Animals; Cell Compartmentation; Cell Membrane; Fatty Acids, Unsaturated; Humans; Membrane Lipids; Metabolic Diseases; Neoplasms; Neurodegenerative Diseases

PubMed: 31052427
DOI: 10.3390/ijms20092167

Review

Authors: Norma W Andrews, Matthias Corrotte

Tissue wound repair has been studied extensively. It involves the coordinated activation of several intracellular and intercellular pathways, as well as remodeling from the sequential recruitment of different cell types to the wound site. There is, however, an equally important process that happens at the single cell level, when the integrity of the plasma membrane is compromised. Individual eukaryotic cells can rapidly repair their plasma membrane after injury, through a process that restores internal homeostasis and prevents cell death. Despite its importance, investigations of this fascinating mechanism have been limited. Only recently have we begun to understand that plasma-membrane repair resembles tissue healing, in the sense that it also involves sequential, highly localized remodeling steps that ultimately eliminate all traces of the injury.

Topics: Animals; Calcium; Calcium Channels; Cell Membrane; Exocytosis; Homeostasis; Humans; Wound Healing

PubMed: 29689221
DOI: 10.1016/j.cub.2017.12.034

Review

Authors: Toshihide Kobayashi, Anant K Menon

The plasma membrane is a ∼4 nm thick phospholipid bilayer that defines the boundary of a cell, segregating internal content from the external environment. Its hydrophobic interior presents a barrier to the exchange of ions and polar solutes between the inside and outside of the cell, as well as to the spontaneous reorientation of lipids between the two leaflets of the bilayer. Specific transport systems, e.g. ion channels and lipid flippases, are needed to enable the passage of these molecules across the plasma membrane at physiologically relevant rates. Although the influential fluid mosaic membrane model of 1972 depicted the membrane as an archipelago of protein islands within a uniform sea of lipids, its micrometer-scale lateral heterogeneity was recognized relatively quickly, evolving into the current picture of structural granularity at the nanoscale.

Topics: Biological Transport; Cell Membrane; Hydrodynamics; Lipid Bilayers; Lipid Metabolism; Lipids; Membrane Microdomains; Membrane Proteins

PubMed: 29689220
DOI: 10.1016/j.cub.2018.01.007

Review

Authors: James B Moseley

Moseley discusses the molecular and mechanical functions of eisosomes - invaginations from the yeast plasma membrane.

Topics: Cell Membrane; Cell Membrane Structures; Fungi; Phosphoproteins; Saccharomyces cerevisiae; Saccharomyces cerevisiae Proteins

PubMed: 29689217
DOI: 10.1016/j.cub.2017.11.073

Review

Authors: Tongtong Zhang, Wei Hu, Wei Chen...

Plasma membrane provides a biophysical and biochemical platform for immune cells to trigger signaling cascades and immune responses against attacks from foreign pathogens or tumor cells. Mounting evidence suggests that the biophysical-chemical properties of this platform, including complex compositions of lipids and cholesterols, membrane tension, and electrical potential, could cooperatively regulate the immune receptor functions. However, the molecular mechanism is still unclear because of the tremendous compositional complexity and spatio-temporal dynamics of the plasma membrane. Here, we review the recent significant progress of dynamical regulation of plasma membrane on immune receptors, including T cell receptor, B cell receptor, Fc receptor, and other important immune receptors, to proceed mechano-chemical sensing and transmembrane signal transduction. We also discuss how biophysical-chemical cues couple together to dynamically tune the receptor's structural conformation or orientation, distribution, and organization, thereby possibly impacting their ligand binding and related signal transduction. Moreover, we propose that electrical potential could potentially induce the biophysical-chemical coupling change, such as lipid distribution and membrane tension, to inevitably regulate immune receptor activation.

Topics: Animals; Binding Sites; Cell Membrane; Chemical Phenomena; Electrophysiological Phenomena; Humans; Mechanical Phenomena; Membrane Lipids; Protein Binding; Receptors, Immunologic; Signal Transduction

PubMed: 33679752
DOI: 10.3389/fimmu.2021.613185

Review

Authors: Thomas R Shaw, Subhadip Ghosh, Sarah L Veatch...

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

Review

Authors: Ken Jacobson, Ping Liu, B Christoffer Lagerholm...

Over the last several decades, an impressive array of advanced microscopic and analytical tools, such as single-particle tracking and nanoscopic fluorescence correlation spectroscopy, has been applied to characterize the lateral organization and mobility of components in the plasma membrane. Such analysis can tell researchers about the local dynamic composition and structure of membranes and is important for predicting the outcome of membrane-based reactions. However, owing to the unresolved complexity of the membrane and the structures peripheral to it, identification of the detailed molecular origin of the interactions that regulate the organization and mobility of the membrane has not proceeded quickly. This Perspective presents an overview of how cell-surface structure may give rise to the types of lateral mobility that are observed and some potentially fruitful future directions to elucidate the architecture of these structures in more molecular detail.

Topics: Cell Membrane; Lipid Bilayers; Membrane Lipids; Membrane Microdomains; Membrane Proteins

PubMed: 31051105
DOI: 10.1016/j.cell.2019.04.018

Review

Authors: Alex G Batrouni, Jeremy M Baskin

Phosphoinositides are an important class of anionic, low abundance signaling lipids distributed throughout intracellular membranes. The plasma membrane contains three phosphoinositides: PI(4)P, PI(4,5)P, and PI(3,4,5)P. Of these, PI(4)P has remained the most mysterious, despite its characterization in this membrane more than a half-century ago. Fortunately, recent methodological innovations at the chemistry-biology interface have spurred a renaissance of interest in PI(4)P. Here, we describe these new toolsets and how they have revealed novel functions for the plasma membrane PI(4)P pool. We examine high-resolution structural characterization of the plasma membrane PI 4-kinase complex that produces PI(4)P, tools for modulating PI(4)P levels including isoform-selective PI 4-kinase inhibitors, and fluorescent probes for visualizing PI(4)P. Collectively, these chemical and biochemical approaches have revealed insights into how cells regulate synthesis of PI(4)P and its downstream metabolites as well as new roles for plasma membrane PI(4)P in non-vesicular lipid transport, membrane homeostasis and trafficking, and cell signaling pathways.

Topics: 1-Phosphatidylinositol 4-Kinase; Cell Membrane; Humans; Molecular Structure; Phosphatidylinositol Phosphates

PubMed: 33965837
DOI: 10.1016/j.bmc.2021.116190

Authors: Xin Chen, Wan-Ting He, Lichen Hu...

Necroptosis and pyroptosis are two forms of programmed cell death with a common feature of plasma membrane rupture. Here we studied the morphology and mechanism of pyroptosis in comparison with necroptosis. Different from necroptosis, pyroptosis undergoes membrane blebbing and produces apoptotic body-like cell protrusions (termed pyroptotic bodies) prior to plasma membrane rupture. The rupture in necroptosis is explosion-like, whereas in pyroptosis it leads to flattening of cells. It is known that the execution of necroptosis is mediated by mixed lineage kinase domain-like (MLKL) oligomers in the plasma membrane, whereas gasdermin-D (GSDMD) mediates pyroptosis after its cleavage by caspase-1 or caspase-11. We show that N-terminal fragment of GSDMD (GSDMD-N) generated by caspase cleavage also forms oligomer and migrates to the plasma membrane to kill cells. Both MLKL and GSDMD-N are lipophilic and the N-terminal sequences of both proteins are important for their oligomerization and plasma membrane translocation. Unlike MLKL which forms channels on the plasma membrane that induces influx of selected ions which osmotically swell the cells to burst, GSDMD-N forms non-selective pores and does not rely on increased osmolarity to disrupt cells. Our study reveals the pore-forming activity of GSDMD and channel-forming activity of MLKL determine different ways of plasma membrane rupture in pyroptosis and necroptosis.

Topics: Amino Acids; Animals; Apoptosis Regulatory Proteins; Cell Line; Cell Membrane; Cell Membrane Permeability; Cell Shape; Humans; Intracellular Signaling Peptides and Proteins; Necrosis; Neoplasm Proteins; Phosphate-Binding Proteins; Protein Kinases; Protein Multimerization; Protein Transport; Pyroptosis; Structure-Activity Relationship

PubMed: 27573174
DOI: 10.1038/cr.2016.100

Review

Authors: Adam Horn, Jyoti K Jaiswal

The plasma membrane forms the physical barrier between the cytoplasm and extracellular space, allowing for biochemical reactions necessary for life to occur. Plasma membrane damage needs to be rapidly repaired to avoid cell death. This relies upon the coordinated action of the machinery that polarizes the repair response to the site of injury, resulting in resealing of the damaged membrane and subsequent remodeling to return the injured plasma membrane to its pre-injury state. As lipids comprise the bulk of the plasma membrane, the acts of injury, resealing, and remodeling all directly impinge upon the plasma membrane lipids. In addition to their structural role in shaping the physical properties of the plasma membrane, lipids also play an important signaling role in maintaining plasma membrane integrity. While much attention has been paid to the involvement of proteins in the membrane repair pathway, the role of lipids in facilitating plasma membrane repair remains poorly studied. Here we will discuss the current knowledge of how lipids facilitate plasma membrane repair by regulating membrane structure and signaling to coordinate the repair response, and will briefly note how lipid involvement extends beyond plasma membrane repair to the tissue repair response.

Topics: Animals; Cell Membrane; Humans; Membrane Lipids; Molecular Structure; Signal Transduction

PubMed: 31610866
DOI: 10.1016/bs.ctm.2019.07.001