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Genes & Diseases Sep 2023Exosomes carry and transmit signaling molecules used for intercellular communication. The generation and secretion of exosomes is a multistep interlocking process that... (Review)
Review
Exosomes carry and transmit signaling molecules used for intercellular communication. The generation and secretion of exosomes is a multistep interlocking process that allows simultaneous control of multiple regulatory sites. Protein molecules, mainly RAB GTPases, cytoskeletal proteins and soluble N-ethylmaleimide-sensitive fusion attachment protein receptor (SNARE), are specifically regulated in response to pathological conditions such as altered cellular microenvironment, stimulation by pathogenic factors, or gene mutation. This interferes with the smooth functioning of endocytosis, translocation, degradation, docking and fusion processes, leading to changes in the secretion of exosomes. Large numbers of secreted exosomes are disseminated by the flow of body fluids and absorbed by the recipient cells. By transmitting characteristic functional proteins and genetic information produced under disease conditions, exosomes can change the physiological state of the recipient cells and their microenvironment. The microenvironment, in turn, affects the occurrence and development of disease. Therefore, this review will discuss the mechanism by which exosome secretion is regulated in cells following the formation of mature secretory multivesicular bodies (MVBs). The overall aim is to find ways to eliminate disease-derived exosomes at their source, thereby providing an important new basis for the clinical treatment of disease.
PubMed: 37492712
DOI: 10.1016/j.gendis.2022.03.021 -
Cells Jan 2019Exosomes are membrane-enclosed entities of endocytic origin, which are generated during the fusion of multivesicular bodies (MVBs) and plasma membranes. Exosomes are... (Review)
Review
Exosomes are membrane-enclosed entities of endocytic origin, which are generated during the fusion of multivesicular bodies (MVBs) and plasma membranes. Exosomes are released into the extracellular milieu or body fluids; this process was reported for mesenchymal, epithelial, endothelial, and different immune cells (B-cells and dendritic cells), and was reported to be correlated with normal physiological processes. The compositions and abundances of exosomes depend on their tissue origins and cell types. Exosomes range in size between 30 and 100 nm, and shuttle nucleic acids (DNA, messenger RNAs (mRNAs), microRNAs), proteins, and lipids between donor and target cells. Pathogenic microorganisms also secrete exosomes that modulate the host immune system and influence the fate of infections. Such immune-modulatory effect of exosomes can serve as a diagnostic biomarker of disease. On the other hand, the antigen-presenting and immune-stimulatory properties of exosomes enable them to trigger anti-tumor responses, and exosome release from cancerous cells suggests they contribute to the recruitment and reconstitution of components of tumor microenvironments. Furthermore, their modulation of physiological and pathological processes suggests they contribute to the developmental program, infections, and human diseases. Despite significant advances, our understanding of exosomes is far from complete, particularly regarding our understanding of the molecular mechanisms that subserve exosome formation, cargo packaging, and exosome release in different cellular backgrounds. The present study presents diverse biological aspects of exosomes, and highlights their diagnostic and therapeutic potentials.
Topics: Animals; Exosomes; Humans; Models, Biological; Proteins
PubMed: 30699987
DOI: 10.3390/cells8020099 -
Stem Cell Research & Therapy May 2022Ocular surface and retinal diseases are widespread problems that cannot be ignored in today's society. However, existing prevention and treatment still have many... (Review)
Review
BACKGROUND
Ocular surface and retinal diseases are widespread problems that cannot be ignored in today's society. However, existing prevention and treatment still have many shortcomings and limitations, and fail to effectively hinder the occurrence and development of them.
MAIN BODY
The purpose of this review is to give a detailed description of the potential mechanism of exosomes and autophagy. The eukaryotic endomembrane system refers to a range of membrane-bound organelles in the cytoplasm that are interconnected structurally and functionally, which regionalize and functionalize the cytoplasm to meet the needs of cells under different conditions. Exosomal biogenesis and autophagy are two important components of this system and are connected by lysosomal pathways. Exosomes are extracellular vesicles that contain multiple signaling molecules produced by multivesicular bodies derived from endosomes. Autophagy includes lysosome-dependent degradation and recycling pathways of cells or organelles. Recent studies have revealed that there is a common molecular mechanism between exosomes and autophagy, which have been, respectively, confirmed to involve in ocular surface and retinal diseases.
CONCLUSION
The relationship between exosomes and autophagy and is mostly focused on fundus diseases, while a deeper understanding of them will provide new directions for the pathological mechanism, diagnosis, and treatment of ocular surface and retinal diseases.
Topics: Autophagy; Exosomes; Extracellular Vesicles; Humans; Lysosomes; Retinal Diseases
PubMed: 35505403
DOI: 10.1186/s13287-022-02854-8 -
International Journal of Biological... 2018Saliva, which contains biological information, is considered a valuable diagnostic tool for local and systemic diseases and conditions because, similar to blood, it... (Review)
Review
Saliva, which contains biological information, is considered a valuable diagnostic tool for local and systemic diseases and conditions because, similar to blood, it contains important molecules like DNA, RNA, and proteins. Exosomes are cell-derived vesicles 30-100 nm in diameter with substantial biological functions, including intracellular communication and signalling. These vesicles, which are present in bodily fluids, including saliva, are released upon fusion of multivesicular bodies (MVBs) with the cellular plasma membrane. Salivary diagnosis has notable advantages, which include noninvasiveness, ease of collection, absence of coagulation, and a similar content as plasma, as well as increased patient compliance compared to other diagnostic approaches. However, investigation of the roles of salivary exosomes is still in its early years. In this review, we first describe the characteristics of endocytosis and secretion of salivary exosomes, as well as database and bioinformatics analysis of exosomes. Then, we describe strategies for the isolation of exosomes from human saliva and the emerging role of salivary exosomes as potential biomarkers of oral and other systemic diseases. Given the ever-growing role of salivary exosomes, defining their functions and understanding their specific mechanisms will provide novel insights into possible applications of salivary exosomes in the diagnosis and treatment of systemic diseases.
Topics: Animals; Biomarkers; Exosomes; Genomics; Humans; Multivesicular Bodies; Saliva; Signal Transduction
PubMed: 29904278
DOI: 10.7150/ijbs.25018 -
Wiener Medizinische Wochenschrift (1946) May 2016This brief overview of endocytic trafficking is written in honor of Renate Fuchs, who retires this year. In the mid-1980s, Renate pioneered studies on the ion-conducting... (Review)
Review
This brief overview of endocytic trafficking is written in honor of Renate Fuchs, who retires this year. In the mid-1980s, Renate pioneered studies on the ion-conducting properties of the recently discovered early and late endosomes and the mechanisms governing endosomal acidification. As described in this review, after uptake through one of many mechanistically distinct endocytic pathways, internalized proteins merge into a common early/sorting endosome. From there they again diverge along distinct sorting pathways, back to the cell surface, on to the trans-Golgi network or across polarized cells. Other transmembrane receptors are packaged into intraluminal vesicles of late endosomes/multivesicular bodies that eventually fuse with and deliver their content to lysosomes for degradation. Endosomal acidification, in part, determines sorting along this pathway. We describe other sorting machinery and mechanisms, as well as the rab proteins and phosphatidylinositol lipids that serve to dynamically define membrane compartments along the endocytic pathway.
Topics: Acid-Base Equilibrium; Animals; Clathrin; Endocytosis; Endosomal Sorting Complexes Required for Transport; Humans; Multivesicular Bodies
PubMed: 26861668
DOI: 10.1007/s10354-016-0432-7 -
Seminars in Cell & Developmental Biology Feb 2018The endosomal sorting complex required for transport (ESCRT) machinery is composed of five multi-subunit protein complexes, which act cooperatively at specialized... (Review)
Review
The endosomal sorting complex required for transport (ESCRT) machinery is composed of five multi-subunit protein complexes, which act cooperatively at specialized endosomes to facilitate the movement of specific cargoes from the limiting membrane into vesicles that bud into the endosome lumen. Over the past decade, numerous proteins, lipids, and RNAs have been shown to be incorporated into intralumenal vesicles (ILVs), but the mechanisms by which these unique cargoes are captured are only now becoming better understood. Here, we discuss the potential roles that the ESCRT machinery plays during cargo sorting at multivesicular endosomes (MVEs).
Topics: Animals; Biological Transport; Endosomal Sorting Complexes Required for Transport; Endosomes; Humans; Multivesicular Bodies
PubMed: 28797838
DOI: 10.1016/j.semcdb.2017.08.020 -
Bioscience Reports Oct 2018Platelets respond to vascular injury via surface receptor stimulation and signaling events to trigger aggregation, procoagulant activation, and granule secretion during... (Review)
Review
Platelets respond to vascular injury via surface receptor stimulation and signaling events to trigger aggregation, procoagulant activation, and granule secretion during hemostasis, thrombosis, and vascular remodeling. Platelets contain three major types of secretory granules including dense granules (or δ-granules, DGs), α-granules (AGs), and lysosomes. The contents of platelet granules are specific. Platelet DGs store polyphosphate and small molecules such as ADP, ATP, Ca, and serotonin, while AGs package most of the proteins that platelets release. The platelet DGs and AGs are regarded as being budded from the endosomes and the -Golgi network (TGN), respectively, and then matured from multivesicular bodies (MVBs). However, the sorting machineries between DGs and AGs are different. Inherited platelet disorders are associated with deficiency of DGs and AGs, leading to bleeding diathesis in patients with Hermansky-Pudlak syndrome (HPS), gray platelet syndrome (GPS), and arthrogryposis, renal dysfunction, and cholestasis syndrome (ARC). Here, we reviewed the current understanding about how DGs differ from AGs in structure, biogenesis, and function. In particular, we focus on the sorting machineries that are involved in the formation of these two types of granules to provide insights into their diverse biological functions.
Topics: Arthrogryposis; Blood Platelets; Cholestasis; Cytoplasmic Granules; Endosomes; Gray Platelet Syndrome; Hermanski-Pudlak Syndrome; Humans; Lysosomes; Multivesicular Bodies; Renal Insufficiency; Secretory Vesicles; trans-Golgi Network
PubMed: 30104399
DOI: 10.1042/BSR20180458 -
Swiss Medical Weekly 2015Exosomes are nanovesicles, generally 50 to 90 nm in diameter, that correspond to the intraluminal vesicles of the endosomal multivesicular bodies and are secreted upon... (Review)
Review
Exosomes are nanovesicles, generally 50 to 90 nm in diameter, that correspond to the intraluminal vesicles of the endosomal multivesicular bodies and are secreted upon fusion of multivesicular bodies with the plasma membrane. Their molecular content is highly selected and includes not only specific proteins and lipids, but also RNA species, such as messenger RNAs (mRNAs) and microRNAs (miRNAs), which are delivered and active in target cells. As they are released in body fluids, exosomes can shuttle molecules for long distances. In the CNS they have been shown to regulate neuronal development and regeneration, and to modulate synaptic functions. In neurodegenerative diseases, they have an important role in propagating neurotoxic misfolded protein from one cell to another and, as recent data show, possibly other molecules contributing to neurotoxicity. Some exosomal lipids such as gangliosides GM1 and GM3 enhance the aggregation of alpha-synuclein, and RNA exosomal cargo is also altered during pathologies such as Alzheimer's disease, prion diseases and amyotrophic lateral sclerosis. The aim of this review is to focus on the regulation of CNS exosomal function and highlight pathways that might have a role in the neurodegenerative process. The identification of the novel exosomal molecules involved in neurodegenerative diseases could provide important insights into the pathogenesis and contribute to the finding of novel diagnostic biomarkers and therapeutic approaches.
Topics: Alzheimer Disease; Central Nervous System; Exosomes; Humans; MicroRNAs; Parkinson Disease; RNA, Messenger
PubMed: 26561744
DOI: 10.4414/smw.2015.14204 -
Cold Spring Harbor Perspectives in... Sep 2013The endosomal sorting complexes required for transport (ESCRT) drive multivesicular body (MVB) biogenesis and cytokinetic abscission. Originally identified through... (Review)
Review
The endosomal sorting complexes required for transport (ESCRT) drive multivesicular body (MVB) biogenesis and cytokinetic abscission. Originally identified through genetics and cell biology, more recent work has begun to elucidate the molecular mechanisms of ESCRT-mediated membrane remodeling, with special focus on the ESCRT-III complex. In particular, several light and electron microscopic studies provide high-resolution imaging of ESCRT-III rings and spirals that purportedly drive MVB morphogenesis and abscission. These studies highlight unifying principles to ESCRT-III function, in particular: (1) the ordered assembly of the ESCRT-III monomers into a heteropolymer, (2) ESCRT-III as a dynamic complex, and (3) the role of the AAA ATPase Vps4 as a contributing factor in membrane scission. Mechanistic comparisons of ESCRT-III function in MVB morphogenesis and cytokinesis suggest common mechanisms in membrane remodeling.
Topics: Cell Membrane; Cytokinesis; Endosomal Sorting Complexes Required for Transport; Models, Biological; Multivesicular Bodies; Signal Transduction
PubMed: 24003212
DOI: 10.1101/cshperspect.a016766 -
Current Opinion in Microbiology Aug 2012Recent advances in secretory biology of African trypanosomes reveal both similarities and striking differences with other model eukaryotic organisms. Secretion is... (Review)
Review
Recent advances in secretory biology of African trypanosomes reveal both similarities and striking differences with other model eukaryotic organisms. Secretion is streamlined for rapid and selective transport of the major cargo, VSG. Selectivity in the early and post-Golgi compartments is dependent on glycosylphosphatidyl inositol anchors. Streamlining includes reduced organellar abundance, and close association of ER exit sites with Golgi and with unique flagellar cytoskeletal elements that govern organellar replication and segregation. These elements include a novel centrin containing bilobe structure. Innate signals for post-Golgi sorting of biosynthetic lysosomal cargo trafficking have been defined, as have pathways for both biosynthetic and endocytic trafficking to the lysosome. Less well-defined secretory organelles such as the multivesicular body and acidocalcisomes are receiving closer scrutiny.
Topics: Animals; Endoplasmic Reticulum; Golgi Apparatus; Humans; Lysosomes; Multivesicular Bodies; Protein Transport; Secretory Pathway; Trypanosoma brucei brucei; Trypanosomiasis, African; Variant Surface Glycoproteins, Trypanosoma
PubMed: 22445359
DOI: 10.1016/j.mib.2012.03.002