scholarly journals Tetraspanins, More than Markers of Extracellular Vesicles in Reproduction

2020 ◽  
Vol 21 (20) ◽  
pp. 7568
Author(s):  
Jana Jankovičová ◽  
Petra Sečová ◽  
Katarína Michalková ◽  
Jana Antalíková
Keyword(s):  
Extracellular Vesicles ◽  
Reproductive System ◽  
Extracellular Vesicle ◽  
Cell Uptake ◽  
Cell Contact ◽  
Cellular Processes ◽  
Pathological Conditions ◽  
Vesicle Biogenesis ◽  
Future Direction ◽  
Insight Into

The participation of extracellular vesicles in many cellular processes, including reproduction, is unquestionable. Although currently, the tetraspanin proteins found in extracellular vesicles are mostly applied as markers, increasing evidence points to their role in extracellular vesicle biogenesis, cargo selection, cell targeting, and cell uptake under both physiological and pathological conditions. In this review, we bring other insight into the involvement of tetraspanin proteins in extracellular vesicle physiology in mammalian reproduction. We provide knowledge regarding the involvement of extracellular vesicle tetraspanins in these processes in somatic cells. Furthermore, we discuss the future direction towards an understanding of their functions in the tissues and fluids of the mammalian reproductive system in gamete maturation, fertilization, and embryo development; their involvement in mutual cell contact and communication in their complexity.

scholarly journals Skeleton-vasculature chain reaction: a novel insight into the mystery of homeostasis

Bone Research ◽  
2021 ◽  
Vol 9 (1) ◽  
Author(s):  
Ming Chen ◽  
Yi Li ◽  
Xiang Huang ◽  
Ya Gu ◽  
Shang Li ◽  
...  
Keyword(s):  
Extracellular Vesicle ◽  
Molecular Regulation ◽  
Research Progress ◽  
Functional Identification ◽  
Paracrine Factors ◽  
New Techniques ◽  
Pathological Conditions ◽  
Endocrine Organs ◽  
Bone Vasculature ◽  
Insight Into

AbstractAngiogenesis and osteogenesis are coupled. However, the cellular and molecular regulation of these processes remains to be further investigated. Both tissues have recently been recognized as endocrine organs, which has stimulated research interest in the screening and functional identification of novel paracrine factors from both tissues. This review aims to elaborate on the novelty and significance of endocrine regulatory loops between bone and the vasculature. In addition, research progress related to the bone vasculature, vessel-related skeletal diseases, pathological conditions, and angiogenesis-targeted therapeutic strategies are also summarized. With respect to future perspectives, new techniques such as single-cell sequencing, which can be used to show the cellular diversity and plasticity of both tissues, are facilitating progress in this field. Moreover, extracellular vesicle-mediated nuclear acid communication deserves further investigation. In conclusion, a deeper understanding of the cellular and molecular regulation of angiogenesis and osteogenesis coupling may offer an opportunity to identify new therapeutic targets.

Dynamin-like proteins are essential for vesicle biogenesis in Mycobacterium tuberculosis

2020 ◽  
Author(s):  
Shamba Gupta ◽  
Ainhoa Palacios ◽  
Atul Khataokar ◽  
Brian Weinrick ◽  
Jose L. Lavín ◽  
...  
Keyword(s):  
Mycobacterium Tuberculosis ◽  
Extracellular Vesicles ◽  
Cell Envelope ◽  
Membrane Vesicle ◽  
Extracellular Vesicle ◽  
Dependent Manner ◽  
Surface Lipid ◽  
Cell Infection ◽  
Vesicle Release ◽  
Vesicle Biogenesis

ABSTRACTMycobacterium tuberculosis (Mtb) secretes pathogenicity factors and immunologically active molecules via membrane vesicles. However, nothing is known about the mechanisms involved in mycobacterial vesicle biogenesis. This study investigates molecular determinants of membrane vesicle production in Mtb by analyzing Mtb cells under conditions of high vesicle production: iron limitation and VirR restriction. Ultrastructural analysis showed extensive cell envelope restructuring in association with vesicle release that correlated with downregulation of cell surface lipid biosynthesis and peptidoglycan alterations. Comparative transcriptomics showed common upregulation of the iniBAC operon in association with high vesicle production in Mtb cells. Vesicle production analysis demonstrated that the dynamin-like proteins (DLPs) encoded by this operon, IniA and IniC, are necessary for release of EV by Mtb in culture and in infected macrophages. Isoniazid, a first-line antibiotic, used in tuberculosis treatment, was found to stimulate vesicle release in a DLP-dependent manner. Our results provide a new understanding of the function of mycobacterial DLPs and mechanistic insights into vesicle biogenesis. The findings will enable further understanding of the relevance of Mtb-derived extracellular vesicles in the pathogenesis of tuberculosis and may open new avenues for therapeutic research.IMPORTANCEIron is an essential nutrient that promotes survival and growth of M. tuberculosis, the bacterium that causes human tuberculosis (TB). Limited availability of iron, often encountered in the host environment, stimulates M. tuberculosis to secrete membrane-bound extracellular vesicles containing molecules that may help it evade the immune system. Characterizing the bacterial factors and mechanisms involved in the production of mycobacterial vesicles is important for envisioning ways to interfere with this process. Here, we report the discovery of proteins required by M. tuberculosis for vesicle biogenesis in culture and during host cell infection. We also demonstrate a connection between antibiotic response and extracellular vesicle production. The work provides insights into the mechanisms underlying vesicle biogenesis in M. tuberculosis and permits better understanding of the significance of vesicle production to M. tuberculosis-host interactions and antibiotic stress response.

scholarly journals Navigating the Landscape of Tumor Extracellular Vesicle Heterogeneity

2019 ◽  
Vol 20 (6) ◽  
pp. 1349 ◽  
Author(s):  
Sabrina Roy ◽  
Hsing-Ying Lin ◽  
Chung-Yu Chou ◽  
Chen-Han Huang ◽  
Julia Small ◽  
...  
Keyword(s):  
Extracellular Vesicles ◽  
Intercellular Communication ◽  
Extracellular Vesicle ◽  
Rapid Expansion ◽  
Parent Cell ◽  
Membrane Composition ◽  
Pathological Conditions ◽  
Respective Parent ◽  
Experimental Level

The last decade has seen a rapid expansion of interest in extracellular vesicles (EVs) released by cells and proposed to mediate intercellular communication in physiological and pathological conditions. Considering that the genetic content of EVs reflects that of their respective parent cell, many researchers have proposed EVs as a source of biomarkers in various diseases. So far, the question of heterogeneity in given EV samples is rarely addressed at the experimental level. Because of their relatively small size, EVs are difficult to reliably isolate and detect within a given sample. Consequently, standardized protocols that have been optimized for accurate characterization of EVs are lacking despite recent advancements in the field. Continuous improvements in pre-analytical parameters permit more efficient assessment of EVs, however, methods to more objectively distinguish EVs from background, and to interpret multiple single-EV parameters are lacking. Here, we review EV heterogeneity according to their origin, mode of release, membrane composition, organelle and biochemical content, and other factors. In doing so, we also provide an overview of currently available and potentially applicable methods for single EV analysis. Finally, we examine the latest findings from experiments that have analyzed the issue at the single EV level and discuss potential implications.

scholarly journals Alcohol Exposure Impacts the Composition of HeLa-Derived Extracellular Vesicles

Biomedicines ◽  
2019 ◽  
Vol 7 (4) ◽  
pp. 78 ◽  
Author(s):  
Leandra B. Jones ◽  
Sanjay Kumar ◽  
Aliyah J. Curry ◽  
Jayde S. Price ◽  
Alexandre Krendelchtchikov ◽  
...  
Keyword(s):  
Extracellular Vesicles ◽  
Hela Cells ◽  
Critical Role ◽  
Alcohol Exposure ◽  
Extracellular Vesicle ◽  
Exosome Biogenesis ◽  
Cancer Line ◽  
Vesicle Biogenesis ◽  
Progression Of Disease ◽  
Shock Proteins

Extracellular vesicles are nanosized vesicles that are under intense investigation for their role in intercellular communication. Extracellular vesicles have begun to be examined for their role in disease protection and their role as disease biomarkers and/or vaccine agents. The goal of this study was to investigate the effects of alcohol exposure on the biogenesis and composition of extracellular vesicles derived from the cervical cancer line, HeLa. The HeLa cells were cultured in exosome-free media and were either mock-treated (control) or treated with 50 mM or 100 mM of alcohol for 24 h and 48 h. Our results demonstrated that alcohol significantly impacts HeLa cell viability and exosome biogenesis/composition. Importantly, our studies demonstrate the critical role of alcohol on HeLa cells, as well as HeLa-derived extracellular vesicle biogenesis and composition. Specifically, these results indicate that alcohol alters extracellular vesicles’ packaging of heat shock proteins and apoptotic proteins. Extracellular vesicles serve as communicators for HeLa cells, as well as biomarkers for the initiation and progression of disease.

scholarly journals Mechanisms of Extracellular Vesicle Biogenesis, Cargo Loading, and Release

2021 ◽  
Author(s):  
Abdel A. Alli
Keyword(s):  
Plasma Membrane ◽  
Circadian Rhythms ◽  
Nucleic Acids ◽  
Extracellular Vesicles ◽  
Extracellular Space ◽  
Extracellular Vesicle ◽  
Apoptotic Bodies ◽  
Endosomal Membranes ◽  
Vesicle Biogenesis

Extracellular vesicles (EVs) are carriers of various biomolecules including bioactive enzymes, lipids, proteins, nucleic acids, and metabolites. EVs are classified into three main types based on their size, biogenesis, and cargo. Exosomes originate from endosomal membranes and are the smallest type of EV. Microvesicles (MVs) or microparticles are larger in size, and like apoptotic bodies which represent the largest type of EVs, both of these vesicles originate from outward budding of the plasma membrane. As discussed in this chapter, cargo loading of EVs and their release into the extracellular space where they can be taken up by neighboring or distant cells plays an important role in physiology and pathophysiology. This chapter will outline specific mechanisms involved in the loading and enrichment of miRNAs, proteins, and lipids within EVs. As explained here, various external and biological stimuli play a role in EV release. Finally, recent studies have shown that the biogenesis, cargo loading, and release of EVs are governed by circadian rhythms. Although EVs were once thought to serve as garbage disposals of cells, the numerous roles they serve in physiology and pathophysiology are now being appreciated.

scholarly journals Emerging Roles of Extracellular Vesicles in the Central Nervous System: Physiology, Pathology, and Therapeutic Perspectives

2021 ◽  
Vol 15 ◽  
Author(s):  
Yadaly Gassama ◽  
Alexandre Favereaux
Keyword(s):  
Central Nervous System ◽  
Nervous System ◽  
Extracellular Vesicles ◽  
Cell Types ◽  
Cellular Processes ◽  
Pathological Conditions ◽  
The Central Nervous System ◽  
System Physiology ◽  
The Brain

Extracellular vesicles or EVs are secreted by most, if not all, eukaryote cell types and recaptured by neighboring or distant cells. Their cargo, composed of a vast diversity of proteins, lipids, and nucleic acids, supports the EVs’ inter-cellular communication. The role of EVs in many cellular processes is now well documented both in physiological and pathological conditions. In this review, we focus on the role of EVs in the central nervous system (CNS) in physiological as well as pathological conditions such as neurodegenerative diseases or brain cancers. We also discuss the future of EVs in clinical research, in particular, their value as biomarkers as well as innovative therapeutic agents. While an increasing number of studies reveal EV research as a promising field, progress in the standardization of protocols and innovation in analysis as well as in research tools is needed to make a breakthrough in our understanding of their impact in the pathophysiology of the brain.

scholarly journals SMPD3-mediated extracellular vesicle biogenesis inhibits oligodendroglioma growth

2020 ◽  
Author(s):  
Anjali Balakrishnan ◽  
Lata Adnani ◽  
Vorapin Chinchalongporn ◽  
Lakshmy Vasan ◽  
Oleksandr Prokopchuk ◽  
...  
Keyword(s):  
Cell Lines ◽  
Extracellular Vesicles ◽  
Extracellular Vesicle ◽  
Driver Mutations ◽  
Lower Grade ◽  
Neoplastic Cells ◽  
Growth Inhibitory ◽  
Vesicle Biogenesis ◽  
Slow Growing

Abstract Oligodendrogliomas are lower-grade, slow-growing gliomas that are ultimately fatal. Although driver mutations are known, the mechanisms underlying their signature slow growth rates are poorly understood. We found evidence for intra-tumoral interactions between neoplastic and non-neoplastic cells in oligodendroglioma tissues. To further study these cell interactions, we used two patient-derived oligodendroglioma cell lines of lower and higher aggressivity. Both oligodendroglioma cell lines released extracellular vesicles that had cytotoxic effects on non-neoplastic and neoplastic cells, but each had distinct vesicular proteomes. Consistent with extracellular vesicles mediating growth inhibitory effects in oligodendrogliomas, higher expression levels of several extracellular vesicle biogenesis genes (SMPD3, TSG101, STAM1) correlates with longer survival in oligodendroglioma patients. Furthermore, SMPD3 overexpression slows oligodendroglioma cell growth in culture. Conversely, SMPD3 knockdown enhances oligodendroglioma proliferation in vitro, in murine xenografts, and in human cerebral organoid co-cultures. Oligodendroglioma-derived extracellular vesicles thus mediate tumor cell microenvironmental interactions that contribute to low aggressivity.

scholarly journals GLI ESOSOMI NELLA COMUNICAZIONE CELLULA-CELLULA

2020 ◽  
Author(s):  
Stefania Raimondo
Keyword(s):  
Small Molecules ◽  
Extracellular Vesicles ◽  
Cell Communication ◽  
Cell Types ◽  
Cell Contact ◽  
Bioactive Lipids ◽  
Pathological Conditions ◽  
Extracellular Matrix Components ◽  
Different Cell Types ◽  
Cell Cell

Cell to cell communication is essential for the coordination and proper organization of different cell types in multicellular systems. Cells exchange information through a multitude of mechanisms such as secreted growth factors and chemokines, small molecules (peptides, ions, bioactive lipids and nucleotides), cell-cell contact and the secretion of extracellular matrix components. Over the last few years a new and sophisticated mechanism of cell-cell communication based on extracellular vesicles has been described. Extracellular vesicles are specialized vesicles released in the extracellular space by most of cell types, under physiological and pathological conditions. Among different extracellular vesicles subtypes, exosomes (30-100 nm) have recently received most of the attention do to their ability to be messenger in intercellular communication.

scholarly journals CDC-derived extracellular vesicles reprogram inflammatory macrophages to an arginase 1-dependent proangiogenic phenotype

2020 ◽  
Vol 318 (6) ◽  
pp. H1447-H1460 ◽  
Author(s):  
Kyle I. Mentkowski ◽  
Asma Mursleen ◽  
Jonathan D. Snitzer ◽  
Lindsey M. Euscher ◽  
Jennifer K. Lang
Keyword(s):  
Myocardial Infarction ◽  
Extracellular Vesicles ◽  
Macrophage Polarization ◽  
Extracellular Vesicle ◽  
Primary Target ◽  
Relevant Model ◽  
M1 Macrophages ◽  
Arginase 1 ◽  
Inflammatory Macrophages ◽  
Insight Into

We hypothesized that in the window of therapeutic extracellular vesicle (EV) administration, inflammatory M1 macrophages are likely the primary target of cardiosphere-derived cell (CDC)-derived EVs. The effect of CDC-EVs on this population, however, is currently unknown. In this study, we demonstrate that CDC-derived EVs polarize M1 macrophages to a proangiogenic phenotype dependent on arginase 1 upregulation. These results provide insight into an immunomodulatory mechanism of CDC-EVs in a more physiologically relevant model of post-myocardial infarction (post-MI) macrophage polarization.

scholarly journals Schistosoma haematobium extracellular vesicle proteins confer protection in a heterologous model of schistosomiasis

2020 ◽  
Author(s):  
Gebeyaw G. Mekonnen ◽  
Bemnet A. Tedla ◽  
Darren Pickering ◽  
Luke Becker ◽  
Lei Wang ◽  
...  
Keyword(s):  
Extracellular Vesicles ◽  
Schistosoma Haematobium ◽  
Extracellular Vesicle ◽  
Surface Proteins ◽  
Helminth Parasites ◽  
Heterologous Challenge ◽  
Host Parasite ◽  
Insight Into ◽  
Host Tissues ◽  
Vesicle Proteins

AbstractHelminth parasites release extracellular vesicles which interact with the surrounding host tissues, mediating host-parasite communication and other fundamental processes of parasitism. As such, vesicle proteins present attractive targets for the development of novel intervention strategies to control these parasites and the diseases they cause. Herein, we describe the first proteomic analysis by LC-MS/MS of two types of extracellular vesicles (exosome-like, 120k pellet vesicles and microvesicle-like, 15k pellet vesicles) from adult Schistosoma haematobium worms. A total of 57 and 330 proteins were identified in the 120k pellet vesicles and larger 15k pellet vesicles, respectively, and some of the most abundant molecules included homologues of known helminth vaccine and diagnostic candidates such as Sm-TSP2, Sm23, glutathione S-tranferase, saposins and aminopeptidases. Tetraspanins were highly represented in the analysis and found in both vesicle types. Vaccination of mice with recombinant versions of three of these tetraspanins induced protection in a heterologous challenge (S. mansoni) model of infection, resulting in significant reductions (averaged across two independent trials) in liver (47%, 38% and 41%) and intestinal (47%, 45% and 41%) egg burdens. These findings offer insight into the mechanisms by which anti-tetraspanin antibodies confer protection and highlight the potential that extracellular vesicle surface proteins offer as anti-helminth vaccines.

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