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Annual Review of Microbiology Oct 2021Secretion of cellular components across the plasma membrane is an essential process that enables organisms to interact with their environments. Production of... (Review)
Review
Secretion of cellular components across the plasma membrane is an essential process that enables organisms to interact with their environments. Production of extracellular vesicles in bacteria is a well-documented but poorly understood process. Outer membrane vesicles (OMVs) are produced in gram-negative bacteria by blebbing of the outer membrane. In addition to their roles in pathogenesis, cell-to-cell communication, and stress responses, OMVs play important roles in immunomodulation and the establishment and balance of the gut microbiota. In this review, we discuss the multiple roles of OMVs and the current knowledge of OMV biogenesis. We also discuss the growing and promising biotechnological applications of OMV.
Topics: Bacterial Outer Membrane; Bacterial Outer Membrane Proteins; Cell Membrane; Extracellular Vesicles; Gram-Negative Bacteria
PubMed: 34351789
DOI: 10.1146/annurev-micro-052821-031444 -
Proceedings of the National Academy of... May 2023Integral membrane protein structure determination traditionally requires extraction from cell membranes using detergents or polymers. Here, we describe the isolation and...
Integral membrane protein structure determination traditionally requires extraction from cell membranes using detergents or polymers. Here, we describe the isolation and structure determination of proteins in membrane vesicles derived directly from cells. Structures of the ion channel Slo1 from total cell membranes and from cell plasma membranes were determined at 3.8 Å and 2.7 Å resolution, respectively. The plasma membrane environment stabilizes Slo1, revealing an alteration of global helical packing, polar lipid, and cholesterol interactions that stabilize previously unresolved regions of the channel and an additional ion binding site in the Ca regulatory domain. The two methods presented enable structural analysis of both internal and plasma membrane proteins without disrupting weakly interacting proteins, lipids, and cofactors that are essential to biological function.
Topics: Membrane Proteins; Cell Membrane; Ion Channels; Binding Sites
PubMed: 37098056
DOI: 10.1073/pnas.2302325120 -
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 -
International Journal of Molecular... Jul 2017Studying organelles in isolation has been proven to be indispensable for deciphering the underlying mechanisms of molecular cell biology. However, observing organelles... (Review)
Review
Studying organelles in isolation has been proven to be indispensable for deciphering the underlying mechanisms of molecular cell biology. However, observing organelles in intact cells with the use of microscopic techniques reveals a new set of different junctions and contact sites between them that contribute to the control and regulation of various cellular processes, such as calcium and lipid exchange or structural reorganization of the mitochondrial network. In recent years, many studies focused their attention on the structure and function of contacts between mitochondria and other organelles. From these studies, findings emerged showing that these contacts are involved in various processes, such as lipid synthesis and trafficking, modulation of mitochondrial morphology, endoplasmic reticulum (ER) stress, apoptosis, autophagy, inflammation and Ca 2 + handling. In this review, we focused on the physical interactions of mitochondria with the endoplasmic reticulum and plasma membrane and summarized present knowledge regarding the role of mitochondria-associated membranes in calcium homeostasis and lipid metabolism.
Topics: Animals; Apoptosis; Biological Transport; Calcium; Cell Membrane; Disease Susceptibility; Endoplasmic Reticulum; Homeostasis; Humans; Lipid Metabolism; Mitochondria; Mitochondrial Dynamics; Protein Transport
PubMed: 28726733
DOI: 10.3390/ijms18071576 -
Current Biology : CB Apr 2018Caveolae are one of the most abundant and striking features of the plasma membrane of many mammalian cell types. These surface pits have fascinated biologists since... (Review)
Review
Caveolae are one of the most abundant and striking features of the plasma membrane of many mammalian cell types. These surface pits have fascinated biologists since their discovery by the pioneers of electron microscopy in the middle of the last century, but we are only just starting to understand their multiple functions. Molecular understanding of caveolar formation is advancing rapidly and we now know that sculpting the membrane to generate the characteristic bulb-shaped caveolar pit involves the coordinated action of integral membrane proteins and peripheral membrane coat proteins in a process dependent on their multiple interactions with membrane lipids. The resulting structure is further stabilised by protein complexes at the caveolar neck. Caveolae can bud to generate an endocytic carrier but can also be disassembled in response to specific stimuli to function as a mechanoprotective device. These structures have also been linked to numerous signalling pathways. Here, we will briefly summarise the current molecular and structural understanding of caveolar formation and dynamics, discuss how the crucial structural components of caveolae work together to generate a dynamic sensing domain, and discuss the implications of recent studies on the diverse roles proposed for caveolae in different cells and tissues.
Topics: Animals; Caveolae; Caveolins; Cell Membrane; Cell Membrane Structures; Humans; Mammals; Membrane Lipids; Membrane Proteins; Signal Transduction
PubMed: 29689223
DOI: 10.1016/j.cub.2017.11.075 -
International Journal of Molecular... Apr 2020Beyond the consolidated role in degrading and recycling cellular waste, the autophagic- and endo-lysosomal systems play a crucial role in extracellular release pathways.... (Review)
Review
Beyond the consolidated role in degrading and recycling cellular waste, the autophagic- and endo-lysosomal systems play a crucial role in extracellular release pathways. Lysosomal exocytosis is a process leading to the secretion of lysosomal content upon lysosome fusion with plasma membrane and is an important mechanism of cellular clearance, necessary to maintain cell fitness. Exosomes are a class of extracellular vesicles originating from the inward budding of the membrane of late endosomes, which may not fuse with lysosomes but be released extracellularly upon exocytosis. In addition to garbage disposal tools, they are now considered a cell-to-cell communication mechanism. Autophagy is a cellular process leading to sequestration of cytosolic cargoes for their degradation within lysosomes. However, the autophagic machinery is also involved in unconventional protein secretion and autophagy-dependent secretion, which are fundamental mechanisms for toxic protein disposal, immune signalling and pathogen surveillance. These cellular processes underline the crosstalk between the autophagic and the endosomal system and indicate an intersection between degradative and secretory functions. Further, they suggest that the molecular mechanisms underlying fusion, either with lysosomes or plasma membrane, are key determinants to maintain cell homeostasis upon stressing stimuli. When they fail, the accumulation of undigested substrates leads to pathological consequences, as indicated by the involvement of autophagic and lysosomal alteration in human diseases, namely lysosomal storage disorders, age-related neurodegenerative diseases and cancer. In this paper, we reviewed the current knowledge on the functional role of extracellular release pathways involving lysosomes and the autophagic- and endo-lysosomal systems, evaluating their implication in health and disease.
Topics: Animals; Autophagy; Cell Membrane; Endosomes; Exocytosis; Exosomes; Extracellular Vesicles; Humans; Lysosomes
PubMed: 32276321
DOI: 10.3390/ijms21072576 -
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 -
The Journal of Biological Chemistry Oct 2021Mitochondria are known as the powerhouses of eukaryotic cells; however, they perform many other functions besides oxidative phosphorylation, including Ca homeostasis,... (Review)
Review
Mitochondria are known as the powerhouses of eukaryotic cells; however, they perform many other functions besides oxidative phosphorylation, including Ca homeostasis, lipid metabolism, antiviral response, and apoptosis. Although other hypotheses exist, mitochondria are generally thought as descendants of an α-proteobacteria that adapted to the intracellular environment within an Asgard archaebacteria, which have been studied for decades as an organelle subdued by the eukaryotic cell. Nevertheless, several early electron microscopy observations hinted that some mitochondria establish specific interactions with certain plasma membrane (PM) domains in mammalian cells. Furthermore, recent findings have documented the direct physical and functional interaction of mitochondria and the PM, the organization of distinct complexes, and their communication through vesicular means. In yeast, some molecular players mediating this interaction have been elucidated, but only a few works have studied this interaction in mammalian cells. In addition, mitochondria can be translocated among cells through tunneling nanotubes or by other mechanisms, and free, intact, functional mitochondria have been reported in the blood plasma. Together, these findings challenge the conception of mitochondria as organelles subdued by the eukaryotic cell. This review discusses the evidence of the mitochondria interaction with the PM that has been long disregarded despite its importance in cell function, pathogenesis, and evolution. It also proposes a scheme of mitochondria-PM interactions with the intent to promote research and knowledge of this emerging pathway that promises to shift the current paradigms of cell biology.
Topics: Animals; Cell Membrane; Humans; Mitochondria
PubMed: 34481840
DOI: 10.1016/j.jbc.2021.101164