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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 -
Current Biology : CB Apr 2018Exosomes and ectosomes, two distinct types of extracellular vesicles generated by all types of cell, play key roles in intercellular communication. The formation of... (Review)
Review
Exosomes and ectosomes, two distinct types of extracellular vesicles generated by all types of cell, play key roles in intercellular communication. The formation of these vesicles depends on local microdomains assembled in endocytic membranes for exosomes and in the plasma membrane for ectosomes. These microdomains govern the accumulation of proteins and various types of RNA associated with their cytosolic surface, followed by membrane budding inward for exosome precursors and outward for ectosomes. A fraction of endocytic cisternae filled with vesicles - multivesicular bodies - are later destined to undergo regulated exocytosis, leading to the extracellular release of exosomes. In contrast, the regulated release of ectosomes follows promptly after their generation. These two types of vesicle differ in size - 50-150 nm for exosomes and 100-500 nm for ectosomes - and in the mechanisms of assembly, composition, and regulation of release, albeit only partially. For both exosomes and ectosomes, the surface and luminal cargoes are heterogeneous when comparing vesicles released by different cell types or by single cells in different functional states. Upon release, the two types of vesicle navigate through extracellular fluid for varying times and distances. Subsequently, they interact with recognized target cells and undergo fusion with endocytic or plasma membranes, followed by integration of vesicle membranes into their fusion membranes and discharge of luminal cargoes into the cytosol, resulting in changes to cellular physiology. After fusion, exosome/ectosome components can be reassembled in new vesicles that are then recycled to other cells, activating effector networks. Extracellular vesicles also play critical roles in brain and heart diseases and in cancer, and are useful as biomarkers and in the development of innovative therapeutic approaches.
Topics: Animals; Cell Communication; Cell Membrane; Cell-Derived Microparticles; Exocytosis; Exosomes; Extracellular Vesicles; Humans; Membrane Fusion; Multivesicular Bodies; Signal Transduction
PubMed: 29689228
DOI: 10.1016/j.cub.2018.01.059 -
Extracellular vesicles in cardiovascular disease: Biological functions and therapeutic implications.Pharmacology & Therapeutics May 2022Extracellular vesicles (EVs), including exosomes and microvesicles, are lipid bilayer particles naturally released from the cell. While exosomes are formed as... (Review)
Review
Extracellular vesicles (EVs), including exosomes and microvesicles, are lipid bilayer particles naturally released from the cell. While exosomes are formed as intraluminal vesicles (ILVs) of the multivesicular endosomes (MVEs) and released to extracellular space upon MVE-plasma membrane fusion, microvesicles are generated through direct outward budding of the plasma membrane. Exosomes and microvesicles have same membrane orientation, different yet overlapping sizes; their cargo contents are selectively packed and dependent on the source cell type and functional state. Both exosomes and microvesicles can transfer bioactive RNAs, proteins, lipids, and metabolites from donor to recipient cells and influence the biological properties of the latter. Over the last decade, their potential roles as effective inter-tissue communicators in cardiovascular physiology and pathology have been increasingly appreciated. In addition, EVs are attractive sources of biomarkers for the diagnosis and prognosis of diseases, because they acquire their complex cargoes through cellular processes intimately linked to disease pathogenesis. Furthermore, EVs obtained from various stem/progenitor cell populations have been tested as cell-free therapy in various preclinical models of cardiovascular diseases and demonstrate unequivocally encouraging benefits. Here we summarize the findings from recent research on the biological functions of EVs in the ischemic heart disease and heart failure, and their potential as novel diagnostic biomarkers and therapeutic opportunities.
Topics: Biomarkers; Cardiovascular Diseases; Cell Communication; Cell-Derived Microparticles; Exosomes; Extracellular Vesicles; Humans
PubMed: 34687770
DOI: 10.1016/j.pharmthera.2021.108025 -
Cell Stem Cell Oct 2021During embryogenesis, optic vesicles develop from the diencephalon via a multistep process of organogenesis. Using induced pluripotent stem cell (iPSC)-derived human...
During embryogenesis, optic vesicles develop from the diencephalon via a multistep process of organogenesis. Using induced pluripotent stem cell (iPSC)-derived human brain organoids, we attempted to simplify the complexities and demonstrate formation of forebrain-associated bilateral optic vesicles, cellular diversity, and functionality. Around day 30, brain organoids attempt to assemble optic vesicles, which develop progressively as visible structures within 60 days. These optic vesicle-containing brain organoids (OVB-organoids) constitute a developing optic vesicle's cellular components, including primitive corneal epithelial and lens-like cells, retinal pigment epithelia, retinal progenitor cells, axon-like projections, and electrically active neuronal networks. OVB-organoids also display synapsin-1, CTIP-positive myelinated cortical neurons, and microglia. Interestingly, various light intensities could trigger photosensitive activity of OVB-organoids, and light sensitivities could be reset after transient photobleaching. Thus, brain organoids have the intrinsic ability to self-organize forebrain-associated primitive sensory structures in a topographically restricted manner and can allow interorgan interaction studies within a single organoid.
Topics: Cell Differentiation; Embryonic Development; Humans; Induced Pluripotent Stem Cells; Organogenesis; Organoids; Prosencephalon
PubMed: 34407456
DOI: 10.1016/j.stem.2021.07.010 -
Cell May 2015Most cancer cells release heterogeneous populations of extracellular vesicles (EVs) containing proteins, lipids, and nucleic acids. In vitro experiments showed that EV...
Most cancer cells release heterogeneous populations of extracellular vesicles (EVs) containing proteins, lipids, and nucleic acids. In vitro experiments showed that EV uptake can lead to transfer of functional mRNA and altered cellular behavior. However, similar in vivo experiments remain challenging because cells that take up EVs cannot be discriminated from non-EV-receiving cells. Here, we used the Cre-LoxP system to directly identify tumor cells that take up EVs in vivo. We show that EVs released by malignant tumor cells are taken up by less malignant tumor cells located within the same and within distant tumors and that these EVs carry mRNAs involved in migration and metastasis. By intravital imaging, we show that the less malignant tumor cells that take up EVs display enhanced migratory behavior and metastatic capacity. We postulate that tumor cells locally and systemically share molecules carried by EVs in vivo and that this affects cellular behavior.
Topics: Animals; Cell Line, Tumor; Humans; Integrases; Mice; Neoplasm Metastasis; Neoplastic Cells, Circulating; Transport Vesicles
PubMed: 26000481
DOI: 10.1016/j.cell.2015.04.042 -
Cell Oct 2018We have uncovered the existence of extracellular vesicle (EV)-mediated signaling between cell types within the adipose tissue (AT) proper. This phenomenon became evident...
We have uncovered the existence of extracellular vesicle (EV)-mediated signaling between cell types within the adipose tissue (AT) proper. This phenomenon became evident in our attempts at generating an adipocyte-specific knockout of caveolin 1 (cav1) protein. Although we effectively ablated the CAV1 gene in adipocytes, cav1 protein remained abundant. With the use of newly generated mouse models, we show that neighboring endothelial cells (ECs) transfer cav1-containing EVs to adipocytes in vivo, which reciprocate by releasing EVs to ECs. AT-derived EVs contain proteins and lipids capable of modulating cellular signaling pathways. Furthermore, this mechanism facilitates transfer of plasma constituents from ECs to the adipocyte. The transfer event is physiologically regulated by fasting/refeeding and obesity, suggesting EVs participate in the tissue response to changes in the systemic nutrient state. This work offers new insights into the complex signaling mechanisms that exist among adipocytes, stromal vascular cells, and, potentially, distal organs.
Topics: Adipocytes; Animals; Caveolin 1; Cell Line; Cells, Cultured; Endothelial Cells; Endothelium, Vascular; Extracellular Vesicles; Fasting; Male; Mice; Mice, Inbred C57BL; Signal Transduction
PubMed: 30293865
DOI: 10.1016/j.cell.2018.09.005 -
Current Biology : CB Jan 2016Approximately one third of a cell's proteins are destined to function outside the cell's boundaries or while embedded within cellular membranes. Ensuring these proteins... (Review)
Review
Approximately one third of a cell's proteins are destined to function outside the cell's boundaries or while embedded within cellular membranes. Ensuring these proteins reach their diverse final destinations with temporal and spatial accuracy is essential for cellular physiology. In eukaryotes, a set of interconnected organelles form the secretory pathway, which encompasses the terrain that these proteins must navigate on their journey from their site of synthesis on the ribosome to their final destinations. Traffic of proteins within the secretory pathway is directed by cargo-bearing vesicles that transport proteins from one compartment to another. Key steps in vesicle-mediated trafficking include recruitment of specific cargo proteins, which must collect locally where a vesicle forms, and release of an appropriate cargo-containing vessel from the donor organelle (Figure 1). The newly formed vesicle can passively diffuse across the cytoplasm, or can catch a ride on the cytoskeleton to travel directionally. Once the vesicle arrives at its precise destination, the membrane of the carrier merges with the destination membrane to deliver its cargo.
Topics: Animals; COP-Coated Vesicles; Cytoplasm; Humans; Organelles; Protein Transport; Saccharomyces cerevisiae Proteins; Vesicular Transport Proteins
PubMed: 26811885
DOI: 10.1016/j.cub.2015.12.017 -
Current Opinion in Structural Biology Aug 2022Clathrin-mediated endocytosis enables selective uptake of molecules into cells in response to changing cellular needs. It occurs through assembly of coat components... (Review)
Review
Clathrin-mediated endocytosis enables selective uptake of molecules into cells in response to changing cellular needs. It occurs through assembly of coat components around the plasma membrane that determine vesicle contents and facilitate membrane bending to form a clathrin-coated transport vesicle. In this review we discuss recent cryo-electron microscopy structures that have captured a series of events in the life cycle of a clathrin-coated vesicle. Both single particle analysis and tomography approaches have revealed details of the clathrin lattice structure itself, how AP2 may interface with clathrin within a coated vesicle and the importance of PIP2 binding for assembly of the yeast adaptors Sla2 and Ent1 on the membrane. Within cells, cryo-electron tomography of clathrin in flat lattices and high-speed AFM studies provided new insights into how clathrin morphology can adapt during CCV formation. Thus, key mechanical processes driving clathrin-mediated endocytosis have been captured through multiple techniques working in partnership.
Topics: Cell Membrane; Clathrin; Clathrin-Coated Vesicles; Coated Vesicles; Cryoelectron Microscopy; Endocytosis; Saccharomyces cerevisiae
PubMed: 35872561
DOI: 10.1016/j.sbi.2022.102427 -
Current Opinion in Plant Biology Oct 2022Extracellular vesicles (EVs) carrying RNA have attracted growing attention in plant cell biology. For a long time, EV release or uptake through the rigid plant cell wall... (Review)
Review
Extracellular vesicles (EVs) carrying RNA have attracted growing attention in plant cell biology. For a long time, EV release or uptake through the rigid plant cell wall was considered to be impossible and RNA outside cells to be unstable. Identified EV biomarkers have brought new insights into functional roles of EVs to transport their RNA cargo for systemic spread in plants and into plant-invading pathogens. RNA-binding proteins supposedly take over key functions in EV-mediated RNA secretion and transport, but the mechanisms of RNA sorting and EV translocation through the plant cell wall and plasma membrane are not understood. Characterizing the molecular players and the cellular mechanisms of plant RNA-containing EVs will create new knowledge in cell-to-cell and inter-organismal communication.
Topics: Biological Transport; Biomarkers; Cell Communication; Extracellular Vesicles; Plants; RNA, Plant
PubMed: 35964451
DOI: 10.1016/j.pbi.2022.102272 -
Cells Jun 2020Cellular secretion depends on exocytosis of secretory vesicles and discharge of vesicle contents. Actin and myosin are essential for pre-fusion and post-fusion stages of... (Review)
Review
Cellular secretion depends on exocytosis of secretory vesicles and discharge of vesicle contents. Actin and myosin are essential for pre-fusion and post-fusion stages of exocytosis. Secretory vesicles depend on actin for transport to and attachment at the cell cortex during the pre-fusion phase. Actin coats on fused vesicles contribute to stabilization of large vesicles, active vesicle contraction and/or retrieval of excess membrane during the post-fusion phase. Myosin molecular motors complement the role of actin. Myosin V is required for vesicle trafficking and attachment to cortical actin. Myosin I and II members engage in local remodeling of cortical actin to allow vesicles to get access to the plasma membrane for membrane fusion. Myosins stabilize open fusion pores and contribute to anchoring and contraction of actin coats to facilitate vesicle content release. Actin and myosin function in secretion is regulated by a plethora of interacting regulatory lipids and proteins. Some of these processes have been first described in non-neuronal cells and reflect adaptations to exocytosis of large secretory vesicles and/or secretion of bulky vesicle cargoes. Here we collate the current knowledge and highlight the role of actomyosin during distinct phases of exocytosis in an attempt to identify unifying molecular mechanisms in non-neuronal secretory cells.
Topics: Actin Cytoskeleton; Actins; Animals; Exocytosis; Humans; Membrane Fusion; Myosins; Secretory Vesicles
PubMed: 32545391
DOI: 10.3390/cells9061455