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The Journal of Cell Biology Feb 2013Cells release into the extracellular environment diverse types of membrane vesicles of endosomal and plasma membrane origin called exosomes and microvesicles,... (Review)
Review
Cells release into the extracellular environment diverse types of membrane vesicles of endosomal and plasma membrane origin called exosomes and microvesicles, respectively. These extracellular vesicles (EVs) represent an important mode of intercellular communication by serving as vehicles for transfer between cells of membrane and cytosolic proteins, lipids, and RNA. Deficiencies in our knowledge of the molecular mechanisms for EV formation and lack of methods to interfere with the packaging of cargo or with vesicle release, however, still hamper identification of their physiological relevance in vivo. In this review, we focus on the characterization of EVs and on currently proposed mechanisms for their formation, targeting, and function.
Topics: Biological Transport; Cell Communication; Cell Membrane; Exosomes; Membrane Fusion; Models, Biological; Proteins
PubMed: 23420871
DOI: 10.1083/jcb.201211138 -
International Journal of Molecular... May 2019Biological 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... (Review)
Review
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 -
Current Biology : CB Apr 2018Tissue wound repair has been studied extensively. It involves the coordinated activation of several intracellular and intercellular pathways, as well as remodeling from... (Review)
Review
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 -
Current Biology : CB Apr 2018The plasma membrane is a ∼4 nm thick phospholipid bilayer that defines the boundary of a cell, segregating internal content from the external environment. Its... (Review)
Review
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 -
FEBS Letters Nov 2020Plasma membrane carries out multiple physiological functions that require its dynamic and tightly regulated organization into specialized domains of different size,... (Review)
Review
Plasma membrane carries out multiple physiological functions that require its dynamic and tightly regulated organization into specialized domains of different size, stability, and lipid/protein composition. Sphingolipids are a group of lipids in which the plasma membrane is particularly enriched, thus being crucial for its structure and function. A specific type of sphingolipid-enriched plasma membrane domains, where ergosterol is depleted and lipids are tightly packed in a rigid gel phase, has recently been found in several fungal species, including yeasts and moulds. After presenting the main biophysical features of gel domains and the experimental method for their detection in the fungal plasma membrane, we review these sphingolipid-enriched gel domains and illustrate their importance to both unicellular and multicellular fungi. First, the biophysical properties of the fungal sphingolipid-enriched domains will be analysed taking into consideration the plasma membrane sphingolipidome. Next, their possible biological roles will be summarized, including their relations with plasma membrane compartments and involvement in stress responses. Moreover, since the plasma membrane is a target for several antifungal compounds, a biophysical connection between sphingolipid-enriched domains and antifungal action will be explored.
Topics: Carbohydrate Sequence; Cell Membrane; Fungi; Sphingolipids
PubMed: 33141925
DOI: 10.1002/1873-3468.13986 -
Cell Research Sep 2016Necroptosis 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...
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 -
Current Biology : CB Apr 2018Moseley discusses the molecular and mechanical functions of eisosomes - invaginations from the yeast plasma membrane. (Review)
Review
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 -
Human Genetics Aug 2023Exocytosis is the process by which secretory vesicles fuse with the plasma membrane to deliver materials to the cell surface or to release cargoes to the extracellular... (Review)
Review
Exocytosis is the process by which secretory vesicles fuse with the plasma membrane to deliver materials to the cell surface or to release cargoes to the extracellular space. The exocyst-an evolutionarily conserved octameric protein complex-mediates spatiotemporal control of SNARE complex assembly for vesicle fusion and tethering the secretory vesicles to the plasma membrane. The exocyst participates in diverse cellular functions, including protein trafficking to the plasma membrane, membrane extension, cell polarity, neurite outgrowth, ciliogenesis, cytokinesis, cell migration, autophagy, host defense, and tumorigenesis. Exocyst subunits are essential for cell viability; and mutations or variants in several exocyst subunits have been implicated in human diseases, mostly neurodevelopmental disorders and ciliopathies. These conditions often share common features such as developmental delay, intellectual disability, and brain abnormalities. In this review, we summarize the mutations and variants in exocyst subunits that have been linked to disease and discuss the implications of exocyst dysfunction in other disorders.
Topics: Humans; Vesicular Transport Proteins; Cytoplasm; Cell Membrane; Exocytosis; Nervous System Diseases
PubMed: 37085629
DOI: 10.1007/s00439-023-02558-w -
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 -
Philosophical Transactions of the Royal... Aug 2019Cells are constantly submitted to external mechanical stresses, which they must withstand and respond to. By forming a physical boundary between cells and their... (Review)
Review
Cells are constantly submitted to external mechanical stresses, which they must withstand and respond to. By forming a physical boundary between cells and their environment that is also a biochemical platform, the plasma membrane (PM) is a key interface mediating both cellular response to mechanical stimuli, and subsequent biochemical responses. Here, we review the role of the PM as a mechanosensing structure. We first analyse how the PM responds to mechanical stresses, and then discuss how this mechanical response triggers downstream biochemical responses. The molecular players involved in PM mechanochemical transduction include sensors of membrane unfolding, membrane tension, membrane curvature or membrane domain rearrangement. These sensors trigger signalling cascades fundamental both in healthy scenarios and in diseases such as cancer, which cells harness to maintain integrity, keep or restore homeostasis and adapt to their external environment. This article is part of a discussion meeting issue 'Forces in cancer: interdisciplinary approaches in tumour mechanobiology'.
Topics: Cell Membrane; Homeostasis; Humans; Mechanotransduction, Cellular
PubMed: 31431176
DOI: 10.1098/rstb.2018.0221