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International Journal of Molecular... Sep 2022Bone mineralization entails two mineralization phases: primary and secondary mineralization. Primary mineralization is achieved when matrix vesicles are secreted by... (Review)
Review
Bone mineralization entails two mineralization phases: primary and secondary mineralization. Primary mineralization is achieved when matrix vesicles are secreted by osteoblasts, and thereafter, bone mineral density gradually increases during secondary mineralization. Nearby extracellular phosphate ions (PO) flow into the vesicles via membrane transporters and enzymes located on the vesicles' membranes, while calcium ions (Ca), abundant in the tissue fluid, are also transported into the vesicles. The accumulation of Ca and PO in the matrix vesicles induces crystal nucleation and growth. The calcium phosphate crystals grow radially within the vesicle, penetrate the vesicle's membrane, and continue to grow outside the vesicle, ultimately forming mineralized nodules. The mineralized nodules then attach to collagen fibrils, mineralizing them from the contact sites (i.e., collagen mineralization). Afterward, the bone mineral density gradually increases during the secondary mineralization process. The mechanisms of this phenomenon remain unclear, but osteocytes may play a key role; it is assumed that osteocytes enable the transport of Ca and PO through the canaliculi of the osteocyte network, as well as regulate the mineralization of the surrounding bone matrix via the Phex/SIBLINGs axis. Thus, bone mineralization is biologically regulated by osteoblasts and osteocytes.
Topics: Bone Matrix; Calcification, Physiologic; Collagen; Extracellular Matrix; Osteoblasts; Osteocytes
PubMed: 36077336
DOI: 10.3390/ijms23179941 -
Frontiers in Molecular Neuroscience 2023The release of extracellular vesicles is observed across numerous cell types and serves a range of biological functions including intercellular communication and waste... (Review)
Review
The release of extracellular vesicles is observed across numerous cell types and serves a range of biological functions including intercellular communication and waste disposal. One cell type which stands out for its robust capacity to release extracellular vesicles is the vertebrate photoreceptor cell. For decades, the release of extracellular vesicles by photoreceptors has been documented in many different animal models of photoreceptor degeneration and, more recently, in wild type photoreceptors. Here, I review all studies describing extracellular vesicle release by photoreceptors and discuss the most unifying theme among them-a photoreceptor cell fully, or partially, diverts its light sensitive membrane material to extracellular vesicles when it has defects in the delivery or morphing of this material into the photoreceptor's highly organized light sensing organelle. Because photoreceptors generate an enormous amount of light sensitive membrane every day, the diversion of this material to extracellular vesicles can cause a massive accumulation of these membranes within the retina. Little is known about the uptake of photoreceptor derived extracellular vesicles, although in some cases the retinal pigment epithelial cells, microglia, Müller glia, and/or photoreceptor cells themselves have been shown to phagocytize them.
PubMed: 37273908
DOI: 10.3389/fnmol.2023.1182573 -
FEBS Letters Mar 2023COPI-coated vesicles mediate transport between Golgi stacks and retrograde transport from the Golgi to the endoplasmic reticulum. The COPI coat exists as a stable... (Review)
Review
COPI-coated vesicles mediate transport between Golgi stacks and retrograde transport from the Golgi to the endoplasmic reticulum. The COPI coat exists as a stable heptameric complex in the cytosol termed coatomer and is recruited en bloc to the membrane for vesicle formation. Recruitment of COPI onto membranes is mediated by the Arf family of small GTPases, which, in their GTP-bound state, bind both membrane and coatomer. Arf GTPases also influence cargo selection, vesicle scission and vesicle uncoating. Guanine nucleotide exchange factors (GEFs) and GTPase-activating proteins (GAPs) regulate nucleotide binding by Arf GTPases. To understand the mechanism of COPI-coated vesicle trafficking, it is necessary to characterize the interplay between coatomer and Arf GTPases and their effectors. It is also necessary to understand interactions between coatomer and cargo, cargo adaptors/receptors and tethers facilitating binding to the target membrane. Here, we summarize current knowledge of COPI coat protein structure; we describe how structural and biochemical studies contributed to this knowledge; we review mechanistic insights into COPI vesicle biogenesis and disassembly; and we discuss the potential to answer open questions in the field.
Topics: Humans; ADP-Ribosylation Factors; Carrier Proteins; COP-Coated Vesicles; Enzyme Activation; GTPase-Activating Proteins; Guanine Nucleotide Exchange Factors; Substrate Specificity
PubMed: 36513395
DOI: 10.1002/1873-3468.14560 -
Frontiers in Cell and Developmental... 2021
PubMed: 34869394
DOI: 10.3389/fcell.2021.800136 -
Biology Jan 2023Extracellular vesicles (EVs) are cell-derived membrane-surrounded vesicles carrying various types of molecules. These EV cargoes are often used as pathophysiological... (Review)
Review
Extracellular vesicles (EVs) are cell-derived membrane-surrounded vesicles carrying various types of molecules. These EV cargoes are often used as pathophysiological biomarkers and delivered to recipient cells whose fates are often altered in local and distant tissues. Classical EVs are exosomes, microvesicles, and apoptotic bodies, while recent studies discovered autophagic EVs, stressed EVs, and matrix vesicles. Here, we classify classical and new EVs and non-EV nanoparticles. We also review EVs-mediated intercellular communication between cancer cells and various types of tumor-associated cells, such as cancer-associated fibroblasts, adipocytes, blood vessels, lymphatic vessels, and immune cells. Of note, cancer EVs play crucial roles in immunosuppression, immune evasion, and immunotherapy resistance. Thus, cancer EVs change hot tumors into cold ones. Moreover, cancer EVs affect nonimmune cells to promote cellular transformation, including epithelial-to-mesenchymal transition (EMT), chemoresistance, tumor matrix production, destruction of biological barriers, angiogenesis, lymphangiogenesis, and metastatic niche formation.
PubMed: 36671802
DOI: 10.3390/biology12010110 -
International Journal of Molecular... Dec 2022Cells have the ability to communicate with their immediate and distant neighbors through the release of extracellular vesicles (EVs). EVs facilitate intercellular... (Review)
Review
Cells have the ability to communicate with their immediate and distant neighbors through the release of extracellular vesicles (EVs). EVs facilitate intercellular signaling through the packaging of specific cargo in all type of cells, and perturbations of EV biogenesis, sorting, release and uptake is the basis of a number of disorders. In this review, we summarize recent advances of the complex roles of the sphingolipid ceramide and lysosomes in the journey of EV biogenesis to uptake.
Topics: Ceramides; Protein Transport; Extracellular Vesicles; Biological Transport; Lysosomes
PubMed: 36499644
DOI: 10.3390/ijms232315317 -
Autophagy Jul 2023Autophagosome isolation enables the thorough investigation of structural components and engulfed materials. Recently, we introduced a novel antibody-based FACS-mediated...
Autophagosome isolation enables the thorough investigation of structural components and engulfed materials. Recently, we introduced a novel antibody-based FACS-mediated method for isolation of native macroautophagic/autophagic vesicles and confirmed the quality of the preparations. We performed phospholipidomic and proteomic analyses to characterize autophagic vesicle-associated phospholipids and protein cargoes under different autophagy conditions. Lipidomic analyses identified phosphoglycerides and sphingomyelins within autophagic vesicles and revealed that the lipid composition was unaffected by different rates of autophagosome formation. Proteomic analyses identified more than 4500 potential autophagy substrates and showed that in comparison to autophagic vesicles isolated under basal autophagy conditions, starvation only marginally affected the cargo profile. Proteasome inhibition, however, resulted in the enhanced degradation of ubiquitin-proteasome system components. Taken together, the novel isolation method enriched large quantities of autophagic vesicles and enabled detailed analyses of their lipid and cargo composition.
Topics: Autophagy; Proteasome Endopeptidase Complex; Proteomics; Autophagosomes; Lipids
PubMed: 36416088
DOI: 10.1080/15548627.2022.2151188 -
International Journal of Nanomedicine 2023Extracellular vesicles (EVs) are lipid containers that are actively released by cells and contain complex molecular cargoes. These cargoes include abundant material such... (Review)
Review
Extracellular vesicles (EVs) are lipid containers that are actively released by cells and contain complex molecular cargoes. These cargoes include abundant material such as genomes and proteins from cells of origin. They are involved in intercellular communication and various pathological processes, showing excellent potential for diagnosing and treating diseases. Given the significant heterogeneity of EVs in complex physiopathological processes, unveiling their composition is essential to understanding their function. Bulk detection methods have been previously used to analyze EVs, but they often mask their heterogeneity, leading to the loss of valuable information. To overcome this limitation, single extracellular vesicle (SEV) analysis techniques have been developed and advanced. These techniques allow for analyzing EVs' physical information and biometric molecules at the SEV level. This paper reviews recent advances in SEV detection methods and summarizes some clinical applications for SEV detection strategies.
Topics: Extracellular Vesicles; Cell Communication
PubMed: 37750091
DOI: 10.2147/IJN.S421342 -
Radiotherapy and Oncology : Journal of... Apr 2022A review of studies on seminal vesicle motion was performed to improve the understanding of these treatment uncertainties. This will aid planning target volume margin... (Review)
Review
A review of studies on seminal vesicle motion was performed to improve the understanding of these treatment uncertainties. This will aid planning target volume margin reduction, which is necessary for hypofractionation of high-risk prostate cancer. Embase, Medline, Web of science Core collection, Cochrane CENTRAL register of trials and Google scholar were searched for publications including 3D information on seminal vesicle motion. In total 646 publications were found of which 22 publications were eligible for inclusion. The mean, systematic and random error of inter- and intra-fraction translations are reported, as well as rotations. The translations of the seminal vesicles is smallest in the left-right direction, whereas the rotation was largest around this axis. Although rectal and bladder filling status were the main cause for seminal vesicle motion, no apparent effect on magnitude of motion was seen when different bladder and rectal preparation protocols were used. Inter- and intra-fraction motion of the seminal vesicles is significant. In the studies, systematic and random errors range between 1-7 mm and 1-5 mm respectively, and are largely uncorrelated to prostate motion. The maximum correlation between seminal vesicle and prostate motion was reported with an R of 0.7, while 3 other studies report lower and/or non-significant correlations. Five studies report a planning target volume margin of approximately 8 mm. This margin is in line with the results of four relevant dosimetric studies. Mitigating the inter- and intra-fraction motion of the seminal vesicles, including prostate tracking, has the potential to reduce planning target volume margins.
Topics: Humans; Male; Motion; Prostate; Prostatic Neoplasms; Radiotherapy Planning, Computer-Assisted; Seminal Vesicles; Tomography, X-Ray Computed
PubMed: 35157975
DOI: 10.1016/j.radonc.2022.02.002 -
Frontiers in Oncology 2023Extracellular vesicles have undergone a paradigm shift from being considered as 'waste bags' to being central mediators of cell-to-cell signaling in homeostasis and... (Review)
Review
Extracellular vesicles have undergone a paradigm shift from being considered as 'waste bags' to being central mediators of cell-to-cell signaling in homeostasis and several pathologies including cancer. Their ubiquitous nature, ability to cross biological barriers, and dynamic regulation during changes in pathophysiological state of an individual not only makes them excellent biomarkers but also critical mediators of cancer progression. This review highlights the heterogeneity in extracellular vesicles by discussing emerging subtypes, such as migrasomes, mitovesicles, and exophers, as well as evolving components of extracellular vesicles such as the surface protein corona. The review provides a comprehensive overview of our current understanding of the role of extracellular vesicles during different stages of cancer including cancer initiation, metabolic reprogramming, extracellular matrix remodeling, angiogenesis, immune modulation, therapy resistance, and metastasis, and highlights gaps in our current knowledge of extracellular vesicle biology in cancer. We further provide a perspective on extracellular vesicle-based cancer therapeutics and challenges associated with bringing them to the clinic.
PubMed: 37397375
DOI: 10.3389/fonc.2023.1167717