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Cell May 2019Over the last several decades, an impressive array of advanced microscopic and analytical tools, such as single-particle tracking and nanoscopic fluorescence correlation... (Review)
Review
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 -
Current Topics in Membranes 2019The plasma membrane forms the physical barrier between the cytoplasm and extracellular space, allowing for biochemical reactions necessary for life to occur. Plasma... (Review)
Review
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 -
Bioorganic & Medicinal Chemistry Jun 2021Phosphoinositides are an important class of anionic, low abundance signaling lipids distributed throughout intracellular membranes. The plasma membrane contains three... (Review)
Review
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 -
Cancer Metastasis Reviews Jun 2020Flotillins 1 and 2 are two ubiquitous, highly conserved homologous proteins that assemble to form heterotetramers at the cytoplasmic face of the plasma membrane in... (Review)
Review
Flotillins 1 and 2 are two ubiquitous, highly conserved homologous proteins that assemble to form heterotetramers at the cytoplasmic face of the plasma membrane in cholesterol- and sphingolipid-enriched domains. Flotillin heterotetramers can assemble into large oligomers to form molecular scaffolds that regulate the clustering of at the plasma membrane and activity of several receptors. Moreover, flotillins are upregulated in many invasive carcinomas and also in sarcoma, and this is associated with poor prognosis and metastasis formation. When upregulated, flotillins promote plasma membrane invagination and induce an endocytic pathway that allows the targeting of cargo proteins in the late endosomal compartment in which flotillins accumulate. These late endosomes are not degradative, and participate in the recycling and secretion of protein cargos. The cargos of this Upregulated Flotillin-Induced Trafficking (UFIT) pathway include molecules involved in signaling, adhesion, and extracellular matrix remodeling, thus favoring the acquisition of an invasive cellular behavior leading to metastasis formation. Thus, flotillin presence from the plasma membrane to the late endosomal compartment influences the activity, and even modifies the trafficking and fate of key protein cargos, favoring the development of diseases, for instance tumors. This review summarizes the current knowledge on flotillins and their role in cancer development focusing on their function in cellular membrane remodeling and vesicular trafficking regulation.
Topics: Animals; Carcinogenesis; Cell Membrane; Humans; Membrane Microdomains; Membrane Proteins; Neoplasms
PubMed: 32297092
DOI: 10.1007/s10555-020-09873-y -
The FEBS Journal Apr 2022Endocytosis is an essential cellular process required for multiple physiological functions, including communication with the extracellular environment, nutrient uptake,... (Review)
Review
Endocytosis is an essential cellular process required for multiple physiological functions, including communication with the extracellular environment, nutrient uptake, and signaling by the cell surface receptors. In a broad sense, endocytosis is accomplished through either constitutive or ligand-induced invagination of the plasma membrane, which results in the formation of the plasma membrane-retrieved endocytic vesicles, which can either be sent for degradation to the lysosomes or recycled back to the PM. This additional function of endocytosis in membrane retrieval has been adopted by excitable cells, such as neurons, for membrane equilibrium maintenance at synapses. The last two decades were especially productive with respect to the identification of brain-specific functions of the endocytic machinery, which additionally include but not limited to regulation of neuronal differentiation and migration, maintenance of neuron morphology and synaptic plasticity, and prevention of neurotoxic aggregates spreading. In this review, we highlight the current knowledge of brain-specific functions of endocytic machinery with a specific focus on three brain cell types, neuronal progenitor cells, neurons, and glial cells.
Topics: Brain; Cell Membrane; Endocytosis; Lysosomes; Synapses
PubMed: 33896112
DOI: 10.1111/febs.15897 -
The Journal of Physiology Jun 2016Endoplasmic reticulum (ER)-plasma membrane (PM) junctions are contact sites between the ER and the PM; the distance between the two organelles in the junctions is below... (Review)
Review
Endoplasmic reticulum (ER)-plasma membrane (PM) junctions are contact sites between the ER and the PM; the distance between the two organelles in the junctions is below 40 nm and the membranes are connected by protein tethers. A number of molecular tools and technical approaches have been recently developed to visualise, modify and characterise properties of ER-PM junctions. The junctions serve as the platforms for lipid exchange between the organelles and for cell signalling, notably Ca(2+) and cAMP signalling. Vice versa, signalling events regulate the development and properties of the junctions. Two Ca(2+) -dependent mechanisms of de novo formation of ER-PM junctions have been recently described and characterised. The junction-forming proteins and lipids are currently the focus of vigorous investigation. Junctions can be relatively short-lived and simple structures, forming and dissolving on the time scale of a few minutes. However, complex, sophisticated and multifunctional ER-PM junctions, capable of attracting numerous protein residents and other cellular organelles, have been described in some cell types. The road from simplicity to complexity, i.e. the transformation from simple 'nascent' ER-PM junctions to advanced stable multiorganellar complexes, is likely to become an attractive research avenue for current and future junctologists. Another area of considerable research interest is the downstream cellular processes that can be activated by specific local signalling events in the ER-PM junctions. Studies of the cell physiology and indeed pathophysiology of ER-PM junctions have already produced some surprising discoveries, likely to expand with advances in our understanding of these remarkable organellar contact sites.
Topics: Animals; Cell Membrane; Endoplasmic Reticulum; Humans; Intercellular Junctions
PubMed: 26939537
DOI: 10.1113/JP271142 -
Biochimica Et Biophysica Acta Jul 2009The association of tubulin with the plasma membrane comprises multiple levels of penetration into the bilayer: from integral membrane protein, to attachment via... (Review)
Review
The association of tubulin with the plasma membrane comprises multiple levels of penetration into the bilayer: from integral membrane protein, to attachment via palmitoylation, to surface binding, and to microtubules attached by linker proteins to proteins in the membrane. Here we discuss the soundness and weaknesses of the chemical and biochemical evidence marshaled to support these associations, as well as the mechanisms by which tubulin or microtubules may regulate functions at the plasma membrane.
Topics: Cell Membrane; Humans; Hydrophobic and Hydrophilic Interactions; Membrane Proteins; Tubulin
PubMed: 19328773
DOI: 10.1016/j.bbamem.2009.03.013 -
Biophysical Journal Jan 1976In this paper, we develop a theory for viscoelastic behavior of large membrane deformations and apply the analysis to the relaxation of projections produced by small...
In this paper, we develop a theory for viscoelastic behavior of large membrane deformations and apply the analysis to the relaxation of projections produced by small micropipette aspiration of red cell discocytes. We show that this relaxation is dominated by the membrane viscosity and that the cytoplasmic and extracellular fluid flow have negligible influence on the relaxation time and can be neglected. From preliminary data, we estimate the total membrane "viscosity" when the membrane material behaves in an elastic solid manner. The total membrane viscosity is calculated to be 10(-3) dyn-s/cm, which is a surface viscosity that is about three orders of magnitude greater than the surface viscosity of lipid membrane components (as determined by "fluidity" measurements). It is apparent that the lipid bilayer contributes little to the fluid dynamic behavior of the whole plasma membrane and that a structural matrix dominates the viscous dissipation. However, we show that viscous flow in the membrane is not responsible for the temporal dependence of the isotropic membrane tension required to produce lysis and that the previous estimates of Rand, Katchalsky, et al., for "viscosity" are six to eight orders of magnitude too large.
Topics: Animals; Cell Membrane; Elasticity; Erythrocytes; Mathematics; Membranes, Artificial; Models, Biological; Viscosity
PubMed: 1244886
DOI: 10.1016/S0006-3495(76)85658-5 -
Methods in Molecular Biology (Clifton,... 2023Plasma membrane injury activates membrane trafficking and remodeling events that are required for the injured membrane to repair. With the rapidity of the membrane...
Plasma membrane injury activates membrane trafficking and remodeling events that are required for the injured membrane to repair. With the rapidity of the membrane repair process, the repair response needs to be monitored at high temporal and spatial resolution. In this chapter, we describe the use of live cell optical imaging approaches to monitor injury-triggered bulk and individual vesicle endocytosis. Use of these approaches allows quantitatively assessment of the rate of retrieval of the injured plasma membrane by bulk endocytosis as well as by endocytosis of individual caveolae following plasma membrane injury.
Topics: Endocytosis; Cell Membrane; Synaptic Vesicles
PubMed: 36401047
DOI: 10.1007/978-1-0716-2772-3_27 -
The Journal of Cell Biology Feb 2015Biological membranes segregate into specialized functional domains of distinct composition, which can persist for the entire life of the cell. How separation of their... (Review)
Review
Biological membranes segregate into specialized functional domains of distinct composition, which can persist for the entire life of the cell. How separation of their lipid and (glyco)protein components is generated and maintained is not well understood, but the existence of diffusional barriers has been proposed. Remarkably, the physical nature of such barriers and the manner whereby they impede the free diffusion of molecules in the plane of the membrane has rarely been studied in depth. Moreover, alternative mechanisms capable of generating membrane inhomogeneity are often disregarded. Here we describe prototypical biological systems where membrane segregation has been amply documented and discuss the role of diffusional barriers and other processes in the generation and maintenance of their structural and functional compartmentalization.
Topics: Animals; Cell Membrane; Cell Membrane Structures; Cytokinesis; Diffusion; Humans; Membrane Lipids; Membrane Proteins; Protein Transport
PubMed: 25646084
DOI: 10.1083/jcb.201410071