Extracellular vesicles function as complex, membrane-bound carriers that transport proteins, lipids, and nucleic acids between cells, playing vital roles in intercellular communication, developmental biology, and disease pathology, according to recent research. Research into extracellular vesicles reveals a heterogeneous collection of membrane-bound carriers equipped with complex cargos. While early scientific assumptions viewed vesicle release merely as a cellular waste disposal mechanism for nonfunctional components, mounting evidence establishes these structures as sophisticated vehicles for intercellular and interorganismal communication, according to Nih publications. Biochemical Composition and Physiological Roles in Development–>
Extracellular vesicles: unique intercellular delivery vehicles
Extracellular vesicles package diverse payloads, including nucleic acids, lipids, and proteins. These carriers confer stability to their cargo while directing molecules to specific target cell types. Furthermore, vesicular payloads act in a combinatorial manner to deliver complex directives to recipient cells, according to Nih. As detailed in scientific literature, extracellular vesicles are released of varying sizes through both the endosomal pathway and by budding from the plasma membrane. These vesicles are referred to by a variety of names, including exosomes, microvesicles (ectosomes), microparticles and oncosomes, collectively termed extracellular vesicles (EVs). A large amount of work has been directed at understanding their protein and lipid components (see EVpedia: https://www.ncbi.nlm.nih.gov/pubmed/25388151, http://student4.postech.ac.kr/evpedia2_xe/xe/index.php?mid=Home; Vesiclepedia: http://microvesicles.org/browse; and Exocarta: http://exocarta.org/), as well as their physiological relevance. Interest in EVs was recently stoked by the finding that they contain RNA, with the implication that their protein and RNA content might be transferred between cells as a previously unrecognized form of intercellular communication. Initial studies found both mRNAs and non-coding RNAs (ncRNAs), such as miRNAs, stably contained within EVs and showed that these molecules together with other EV cargo could be transferred to recipient cells in culture with functional consequences. During normal development and adult physiology, these vesicles participate directly in cell-to-cell communication. Immune Responses and Neurological Pathologies–>
Virulence and Immunomodulatory Roles of Bacterial Outer Membrane Vesicles
In immunological contexts, the combination of RNA cargo and ligand-receptor interactions across various immune and non-immune cell types shapes complex immune responses. In neuropathology, extracellular vesicles intersect with neurodegenerative disorders such as Parkinson’s disease. Bacterial Outer Membrane Vesicles and Environmental Stress Responses–>
Beyond eukaryotic systems, an ever-growing number of pathogens have been documented to produce and secrete natural OM vesicles. Morphological and biochemical evidence for infected host tissues and fluids supports the idea that the production of vesicles by pathogens occurs during infection and, in fact, may be induced during infection. OM vesicles are closed spheroid particles of a heterogeneous size (∼10 to 300 nm in diameter) released from Gram-negative bacteria during all phases of growth. Electron microscopy studies reveal that OM vesicles are formed from OM bulges and the subsequent fission of vesicles containing electron-dense material, according to Nih source data on bacterial vesicles. Outer membrane vesicles reflect the composition of the bacterial outer membrane, containing lipopolysaccharides, glycerophospholipids, outer membrane proteins, and enclosed periplasmic components. Crucially, these vesicles are not a product of cell death since they contain newly synthesized proteins and are produced without concomitant bacterial lysis. Several OM vesicle proteomes have been evaluated recently, and all were determined to be enriched in envelope components, although some cytosolic and inner membrane proteins were also present in these preparations, according to Nih. All Gram-negative bacteria investigated to date naturally release OM vesicles. Calculations of native OM vesicle production show that the vesicles represent a significant fraction of cellular material. For instance, vesicles produced by typical laboratory cultures of growing and dividing Pseudomonas aeruginosa and Escherichia coli cells account for ∼1% of the OM material in the culture. In contrast, Neisseria meningitidis produces abundant numbers of vesicles, constituting 8 to 12% of radiolabeled protein and endotoxin in log-phase cultures. Not only are OM vesicles produced by free-living cells, they are also abundant in naturally occurring biofilms. In addition, intracellular pathogens such as Legionella pneumophila, Salmonella spp., and Francisella spp. produce OM vesicles in both intraphagosomal and extraphagosomal compartments. In the case of Flavobacterium, vesicles are made late in the growth phase. Vesiculation rates shift in response to environmental factors and cellular stressors. Rates of OM vesicle production are not uniform, even for a particular strain, as production has long been seen to be influenced by environmental factors and by sources of cellular stress. In studies of both nonpathogenic and pathogenic species, vesiculation was found to be upregulated by conditions that activate the σE envelope stress response. In fact, vesiculation appears to be critical to surviving stress. For example, when Pseudomonas fragi contacts pig muscle tissue, bacterial surfaces become covered in vesicles hypothesized to contain proteolytic enzymes that disrupt myofibrils, according to Nih.