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At least 253 records · Page 14Linked to original sources
PubMed1996

SV2proteoglycan: a potential synaptic vesicle transporter and nerve terminal extracellular matrix receptor.

SV2Proteoglycan (SV2pg) is a specific component of small clear synaptic vesicles. It is a keratan sulfate proteoglycan with oligosaccharide side chains N-linked to a core protein of 80 kDa. Two glycosylated forms, H and L, are present in synaptic vesicles. The amino acid sequence suggests that SV2pg contains 12 transmembrane domains and is homologous to bacterial and eukaryotic sugar transporters. Although its structure suggests that SV2pg is a vesicular transporter, what it transports is unknown. SV2pg is probably not a neurotransmitter transporter, since that function resides in an unrelated family of synaptic vesicle proteins. In addition to its vesicular function, SV2pg may have a secondary function as an extracellular matrix (ECM) receptor on the nerve terminal surface. At the electric organ synapse, which is closely related to the neuromuscular junction. SV2pg is bound to laminin, a component of the synaptic ECM. SV2pg is only associated with laminin on the nerve terminal surface, not in the synaptic vesicle. Studies on synaptogenesis during motor nerve regeneration have suggested that nerve terminal ECM receptors play an important role in synaptic recognition.

Animals↗
PubMed2026

Bacterial Outer Membrane Vesicles in Colorectal Cancer: Interdomain Communication Hubs in Pathogenesis and Immunotherapy.

The complex interaction between the intestinal microbiota and host mucosal immunity plays a defining role in colorectal cancer (CRC) development and therapeutic outcomes. Recently, bacterial outer membrane vesicles (OMVs)-nano-sized, lipid-bilayered extracellular particulates released by both commensal and pathogenic microorganisms-have emerged as critical long-range signaling vehicles within the gut. This review provides a comprehensive synthesis of the dual functionalities of OMVs in CRC pathogenesis and oncology. Mechanistically, pathogenic OMVs cross compromised mucosal barriers to drive horizontal gene transfer (HGT) of chimeric episomes, such as SPHINX DNAs and Bovine Meat and Milk Factors (BMMFs), thereby promoting genomic instability and neoplastic transformation. Conversely, there is a paradigm shift toward exploiting next-generation probiotic and engineered OMVs as highly tunable therapeutic platforms. By combining cutting-edge bioengineering strategies-such as biomimetic mineralization to neutralize local tissue acidity and chemotherapeutic packaging-these nanovectors effectively reprogram the immunosuppressive tumor microenvironment (TME). Specifically, optimized OMVs modulate macrophage polarization from an M2 to an M1 phenotype and stimulate CXCL10-mediated CD8+ T-cell infiltration, effectively turning immunologically "cold" tumors "hot." Finally, the great translational challenges regarding systemic endotoxicity, scalability, and target delivery, providing a strategic approach for the integration of OMV-based platforms into synergistic immune checkpoint inhibition regimens.

Colon cancer↗
PubMed2006

Phosphorylation-dependent phospholipase D activity of matrix vesicles.

A progressive hydrolysis of phospholipids was observed during the mineralization process mediated by extracellular matrix vesicles. Increasing levels of different hydrolysis products revealed phospholipase A and D activities. The importance of these enzymes for the mineralization process lies in a high rate of hydrolysis of neutral phospholipids and lower rate of degradation of anionic phospholipids, which may favor mineral formation in vesicular membrane and membrane breakdown necessary for the release of mineral deposits into extracellular matrix. In this report, we focus on the phosphorylation-dependent phospholipase D activity during mineral formation initiated by chicken embryo matrix vesicles.

Animals↗
PubMed2006

Nature of phosphate substrate as a major determinant of mineral type formed in matrix vesicle-mediated in vitro mineralization: An FTIR imaging study.

Membrane-bound extracellular matrix vesicles play an important role in the de novo initiation and propagation of calcium-phosphate mineral formation in calcifying cartilage, bone, dentin, and in pathologic calcification. Characterization of the phase, composition, crystal size, and perfection provides valuable insight into the mechanism of the mineral deposition. In the present study, Fourier transform infrared imaging spectroscopy (FT-IRIS) was used to characterize the mineral phase generated during MV-mediated in vitro mineralization. FT-IRIS studies revealed that the mineral phase associated with MVs calcified in the presence of AMP and beta-GP was always found to be crystalline hydroxyapatite while with ATP only a small amount of immature mineral, most likely an amorphous or poorly crystalline hydroxyapatite, was observed. Low concentrations of pyrophosphate (PPi) (< or = 0.01 mM) showed apatitic mineral while high concentrations showed immature calcium pyrophosphate dihydrate (CPPD). The implications of these findings are that (a) hydrolysis of AMP or beta-GP, monophosphoester substrates of MV-5' AMPase (substrate: AMP) and TNAP (substrates: AMP, beta-GP), yields orthophosphate (Pi) which leads to the formation of mature crystalline, apatite mineral, while the hydrolysis of ATP, substrate for MV-TNAP or ATPase or NPP1, inhibits the formation of mature hydroxyapatite, and (b) pyrophosphate (PPi) has a bimodal effect on mineralization, i.e., at low PPi concentrations, alkaline phosphatase activity of matrix vesicles is able to hydrolyze PPi to orthophosphate and thus facilitates the formation of basic calcium phosphate mineral which subsequently transforms into apatitic mineral. We hypothesize that, at high PPi concentrations, PPi by itself or Pi released by partial PPi hydrolysis could act as inhibitors of alkaline phosphatase activity, thereby preventing complete hydrolysis of PPi to Pi, and thus resulting in the accumulation of calcium pyrophosphate dihydrate. Therefore, in order for physiological mineralization to proceed, a balance is required between levels of Pi and PPi.

Animals↗
PubMed1984

The extracellular matrix between the optic vesicle and presumptive lens during lens morphogenesis in an anophthalmic strain of mice.

Extracellular matrix material present during early lens morphogenesis in anophthalmic strain ZRDCT-Ch mice was studied histochemically by the Alcian blue 8GX pH 2.5, Alcian blue 8GX pH 2.5/periodic acid-Schiff combined, high iron diamine, and Van Gieson methods. Observed staining patterns were compared with results from an analysis of a normal strain of mice (E.H. Webster, Jr., A.F. Silver, and N.I. Gonsalves, 1983, Develop. Biol. 100, 147-157). No differences in constituents were found between the strains in staining patterns of the ectodermal basal lamina. However, the optic vesicle basal lamina in the anophthalmic strain was found to have a relatively lower staining intensity for sulfated glycosaminoglycan associated with it than was observed in the normal strain, although these mutant optic vesicles were morphologically normal. Results from this and the earlier study on normal mice indicate that one function of sulfated glycosaminoglycan in early lens morphogenesis may be to serve as a cementing medium between the optic and lens rudiments. This sulfated glycosaminoglycan deficiency on the anophthalmic optic vesicle basal lamina is temporally correlated with and may be causally related to precocious lens cup formation and frequently observed separation of the normally adherent eye rudiments. Conclusions drawn from this study are consistent with the speculation of H.B. Chase and E.B. Chase (1941, J. Morphol. 68, 279-301) that there may be abnormal contact between the optic vesicle and presumptive lens ectoderm in the mutant strain, although there is a differing view on the cause of the abnormal contact.

Animals↗
PubMed1998

On the origin of membrane vesicles in gram-negative bacteria.

It is proposed that the genesis of extracellular membrane vesicles in Gram-negative bacteria is a result of cell wall turnover. Peptidoglycan turnover would cause a turgor on the outer membrane, causing the outer membrane to bulge and finally bleb. Mechanical motion would then shear the blebs into the culture medium.

Bacterial Outer Membrane Proteins↗
PubMed1990

The effect of glass-ceramic implants on matrix vesicle calcification after two weeks of rat tibial bone healing.

Type, size and distribution of extracellular matrix vesicles (MV), known mediators of primary calcification, were studied around bone-bonding and metal-oxide containing, nonbonding, glass-ceramic implants. This was performed in order to further understand the different effects of implants on bone healing. At 14 days after implantation in adult rat tibial bone the effects of different implants on MV were studied by transmission electron microscopy and computerized morphometry. A total number of 4607 MV in 245 electron micrographs were counted and grouped according to diameter, distance from the calcifying front, and classified as four types: "empty," "amorphous," "crystal," and "rupture." The sequence of types according to diameter and distance was recorded as follows around both implants tested: "rupture" MV were the closest to the front with the largest diameter, followed by "crystal," "amorphous," and "empty," MV with the largest distance from the front and the smallest diameter. Most vesicles were concentrated in a distance of less than 2.4 microns from the front and between diameters of 0.06 microns and 0.22 microns. The noncalcified extracellular matrix around bone-bonding implants contained more MV than the matrix around the nonbonding type (26.24 MV/10 microns2 and 18.76 MV/10 microns2). MV distribution according to types showed that around bonding implants there was a higher percentage of "crystal" and a lower percentage of "rupture" when compared to the nonbonding type. These results indicate that bonding implants affect osteoblastic function by increasing the vesicular number and retardation of intravesicular crystal formation. It might be suggested that bonding implants induce an increase in the process of primary calcification and a decreased rate of crystal formation resulting with the highest organization of the healing bone.

Animals↗
PubMed1990

Cathepsin D in breast cancer cells can digest extracellular matrix in large acidic vesicles.

In breast cancer cell lines, pro-cathepsin D is synthesized in excess and abnormally processed, resulting in its slower maturation and increased secretion into the culture medium. Since this lysosomal protease is only active at acidic pH, we have searched for acidic compartments other than lysosomes where cathepsin D might be active when MCF7 cells are plated on corneal extracellular matrix. We found large acidic intracellular vesicles (1.5 to 20 microns in diameter) by acridine orange and 3-(2,4-dinitroanilino)-3'-amino-N-methyldipropylamine staining, two fluorescent probes which reveal acidic compartments. These vesicles were actively acidified. They were 2- to 20-fold more abundant in MCF7 breast cancer cells and primary cultures of human breast cancers cells than in primary cultures of normal mammary epithelial cells. In living MCF7 cells, high resolution video-enhanced microscopy showed that these vesicles were mobile and intracellular. Double immunolocalization indicated that they contained mature cathepsin D (but no detectable pro-cathepsin D) and endocytosed extracellular material. This material (dextran, transferrin, and extracellular matrix) and the association with other lysosomal enzymes varied according to the vesicles, suggesting their heterogeneity (large endosomes or phagosomes). We conclude that, in breast cancer cells, cathepsin D may digest intracellularly phagocytosed and/or endocytosed extracellular matrix in large acidic vesicles. We propose that the higher expression of cathepsin D associated with the increased number of large acidic vesicles in breast cancer cells may facilitate digestion of basement membrane and consequently metastasis.

Breast Neoplasms↗
PubMedDate not supplied

The amount and proteolytic content of vesicles shed by human cancer cell lines correlates with their in vitro invasiveness.

Cancer cells are known to shed extracellular membrane vesicles both in vitro and in vivo. To analyse their possible involvement in the metastatic behaviour of tumours, we measured the Matrigel invasion capability and amounts of vesicles shed by four human tumour cell lines (8701-BC, MCF-7, MDA-MB-231 and HT-1080), and by MCF-10A, an immortalised human breast cell line. The proteolytic activity content of vesicles was analysed by gelatin and casein zymographies. While MCF-10A cells do not release a measurable amount of vesicles, all tumour lines analysed, when cultured in presence of serum, shed vesicles rich in MMP-9. Other vesicle-associated proteinases include MMP-2 and uPA. Amounts and proteolytic activities of shed vesicles correlate with the in vitro invasiveness of cells. Since vesicles appear to promote the proteolytic cascade required for the localised degradation of the extracellular matrix, their shedding from cancer cells might represent an important feature of tumour progression.

Breast Neoplasms↗
PubMed2005

The role of matrix vesicles in growth plate development and biomineralization.

Skeletal cells control the initiation of mineralization in vivo and determine the selective distribution pattern of mineralization by releasing calcification-initiating, submicroscopic, extracellular matrix vesicles (MVs) at selected sites in the extracellular matrix. The overall objective of this review is to outline what is currently known about the mechanisms of MV biogenesis and mineral initiation, while emphasizing recent observations that enhance our understanding of these mechanisms. Data from studies on the general mechanism of biogenesis of outer membrane vesicles and the formation and function of non-skeletal matrix vesicles is presented to stimulate thought concerning the possible biological functions that these structures may share with MVs.

Alkaline Phosphatase↗
PubMed1979

Matrix vesicles in chicken epiphyseal cartilage. Separation from lysosomes and the distribution of inorganic pyrophosphatase activity.

The extracellular matrix vesicles from epiphyseal cartilage of chickens were isolated by differential centrifugation. The matrix vesicles obtained showed considerable activity of lysosomal enzymes. This appears to have been due to lysosomal contamination because when we used a new density gradient medium (Percoll), the lysosomal enzyme activities and the activity of alkaline phosphatase could be totally separated. Electron microscopy of the alkaline phosphatase-rich fraction showed matrix vesicle-like structures. Phosphatase activities of the cells and matrix vesicles were further studied by Sephadex G-200 gel filtration. Specific magnesium-activated inorganic pyrophosphatase, distinct from nonspecific alkaline phosphatase, could be demonstrated in the cellular fraction. No such separate activity could be demonstrated in the matrix vesicle fraction, and it is supposed that the pyrophosphatase activity in the matrix vesicles originates from the alkaline phosphate.

Alkaline Phosphatase↗
PubMed1984

The fine structure of psammoma bodies in meningocytic whorls.

Psammoma bodies within meningocytic whorls in five cases of meningioma were examined by electron microscopy. The cells comprising the meningocytic whorls showed the conventional ultrastructural features of meningothelial cells with interdigitations and interconnections by means of junctional complexes. In some whorls, collagen fibers, elastic fibers, microfibrils, as well as finely reticulated material were observed. Calcified foci of various sizes were seen within many of these whorls. Extracellular matrix vesicles, with or without hydroxyapatite crystals, were occasionally noted at the periphery of extracellular psammoma bodies in the whorl. Furthermore, many small aggregates of crystals were present adjacent and parallel to the collagen and elastic fibers in the meningocytic whorls. Substantial amounts of collagen fibers were also observed within the large psammoma bodies. These findings suggest that the matrix vesicles, presumably produced by the meningothelial cell, may serve as the initial nidi of calcification of psammoma bodies as originally suggested by Lipper et al. Collagen fibers as well as elastic fibers in the whorls may also play an important role in orienting apatite crystal deposition during the growth of extracellular psammoma bodies and serve as early sites of calcification.

Adult↗
PubMed1995

Molecular biology of matrix vesicles.

Matrix vesicles are extracellular 100-nanometer-diameter membrane-invested particles selectively located within the matrix of bone, cartilage, and predentin. They serve as the initial site of calcification in all skeletal tissues. Matrix vesicle biogenesis occurs by polarized budding and pinching off of vesicles from specific regions of the outer plasma membrane of chondrocytes, osteoblasts, and odontoblasts. Seeding of selected areas of matrix with matrix vesicles explains the localized distribution of subsequent zones of mineralization. Matrix vesicle biogenesis in the growth plate is linked to the chondrocyte cell cycle and reflects a stage in programmed cell death (apoptosis). Generation of initial hydroxyapatite mineral crystals occurs within the matrix vesicle membrane during Phase 1 of biologic mineralization. Phase 1 is controlled by phosphatases (including alkaline phosphatase) and Ca-binding molecules with which the matrix vesicles are well endowed. Phase 2 of biologic mineralization begins with breakdown of matrix vesicle membranes, exposing preformed hydroxyapatite to the extracellular fluid after which mineral crystal proliferation is governed by extracellular conditions. Phase 1 and Phase 2 of mineralization are under cellular control. Phase 1 is initiated by cells generating calcifiable matrix vesicles and releasing them into sites of intended calcification. Phase 2 is controlled by cells regulating extracellular ionic conditions and matrix composition.

Alkaline Phosphatase↗
PubMed1992

Cell maturation-specific autocrine/paracrine regulation of matrix vesicles.

Matrix vesicles are extracellular organelles produced with distinctive phospholipid composition and enzyme activity. They are produced by cells which typically calcify their extracellular matrix and their characteristics are cell-maturation dependent. Regulation of matrix vesicle structure and function occurs at the genomic and non-genomic levels. By following alkaline phosphatase gene transcription, protein concentration, and enzyme specific activity, we have shown that steroid hormones and growth factors exhibit a regulatory influence over gene transcription, protein synthesis, and matrix vesicle activity. Matrix vesicles respond to peptide hormones, other matrix proteins, like alpha 2-HS-glycoprotein, and autocoid mediators as well. Matrix vesicle metabolism can be directly affected by vitamin D metabolites, even in the absence of cells. The results indicate that 1,25-(OH)2D3(1,25D) or 24,25-(OH)2D3(24,25D) produced by the cells in culture can modulate matrix vesicle activity, and suggest that calcifying cells can modulate events in the matrix via autocrine/paracrine stimulation or inhibition of the matrix vesicles. 1,25D and 24,25D regulate matrix vesicle phospholipase A2 activity, fatty acid turnover, arachidonic acid release, PGE2 production and membrane fluidity, which act on the matrix vesicle to alter enzyme activity. Since vitamin D metabolite production is sensitive to both hormones and growth factors, there is potential for fine tuning matrix vesicle behavior.

Animals↗
PubMed2005

Exosomes contain ubiquitinated proteins.

Multivesicular bodies (MVB) are endosomal compartments that contain multiple vesicles, which derive from a delimiting membrane by inward budding. Incorporation of membrane proteins into the luminal vesicles requires, at least for some model proteins, monoubiquitination of their cytoplasmic domain. The ubiquitin tags are recognized by a sorting machinery, of which some components are also monoubiquitinated. The ubiquitin tags and the sorting machinery are both removed before the vesicles bud into the MVB lumen. MVB vesicles are therefore not expected to contain monoubiquitinated proteins. The MVB content is degraded upon fusion of MVB with lysosomes. In many cell types, however, MVB can also fuse with the plasma membrane, resulting in secretion of their luminal vesicles into the extracellular milieu. Such secreted vesicles are termed exosomes, and their protein composition should, due to their origin, be identical to that of MVB luminal vesicles. We here demonstrate that exosomes contain polyubiquitinated proteins, many of which are not integrated into the membrane and relatively enriched as compared to total cell lysates. These results suggest that a subset of polyubiquitinated cytoplasmic proteins is incorporated into the MVB pathway. The potential cell biological relevance of this observation is discussed. Furthermore, these data indicate that ubiquitinated proteins can serve as markers for exosomes.

Animals↗
PubMed1998

Selective enrichment of tetraspan proteins on the internal vesicles of multivesicular endosomes and on exosomes secreted by human B-lymphocytes.

Association of major histocompatibility complex (MHC) class II molecules with peptides occurs in a series of endocytic vacuoles, termed MHC class II-enriched compartments (MIICs). Morphological criteria have defined several types of MIICs, including multivesicular MIICs, which are composed of 50-60-nm vesicles surrounded by a limiting membrane. Multivesicular MIICs can fuse with the plasma membrane, thereby releasing their internal vesicles into the extracellular space. The externalized vesicles, termed exosomes, carry MHC class II and can stimulate T-cells in vitro. In this study, we show that exosomes are enriched in the co-stimulatory molecule CD86 and in several tetraspan proteins, including CD37, CD53, CD63, CD81, and CD82. Interestingly, subcellular localization of these molecules revealed that they were concentrated on the internal membranes of multivesicular MIICs. In contrast to the tetraspans, other membrane proteins of MIICs, such as HLA-DM, Lamp-1, and Lamp-2, were mainly localized to the limiting membrane and were hardly detectable on the internal membranes of MIICs nor on exosomes. Because internal vesicles of multivesicular MIICs are thought to originate from inward budding of the limiting membrane, the differential distribution of membrane proteins on the internal and limiting membranes of MIICs has to be driven by active protein sorting.

Antigens, CD↗
PubMed2006

Membrane vesicles released by Avibacterium paragallinarum contain putative virulence factors.

Avibacterium paragallinarum, the causative agent of infectious coryza, releases extracellular membrane vesicles (MVs), containing immunogenic proteins, proteases, putative RTX proteins, haemagglutinin, and nucleic acids, into the medium. MVs ranging 50-300 nm in diameter were observed by electron microscopy. They contained immunogenic proteins in the range of 20-160 kDa, detected using vaccinated or experimentally infected chicken sera raised against Av. paragallinarum, but not in pooled sera from specific pathogen-free chickens. Proteolytic activity was not detected in MVs through zymograms; however, immune recognition of high molecular mass bands was observed by Western blotting using an antiprotease serum against Actinobacillus pleuropneumoniae serotype 1 purified protease, suggesting its presence. MVs agglutinated glutaraldehyde-fixed chicken red blood cells indicating the presence of haemagglutinating antigens. Nucleic acids were also detected inside MVs. Avibacterium paragallinarum releases MVs containing putative virulence factors, which could be important in the pathogenesis of infectious coryza.

Animals↗