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 28,634 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Furin is a membrane-associated endoprotease that efficiently cleaves precursor proteins on the C-terminal side of the consensus sequence, Arg-X-Lys/Arg-Arg1, and has been proposed to catalyze these reactions in both exocytic and endocytic compartments. To study its biosynthesis and routing, a furin construct (designated fur/f) containing the FLAG epitope tag inserted on the C-terminal side of the enzyme's autoproteolytic maturation site was used. Introduction of the epitope tag had no effect on the expression, proteolytic maturation or activity of furin. Analysis of the localization of fur/f by immunofluorescence microscopy showed that its staining pattern largely overlapped with those of several Golgi-associated markers. Treatment of cells with brefeldin A caused the fur/f distribution to collapse around the microtubule organizing center, indicating that furin is concentrated in the trans-Golgi network (TGN). Immunoelectron microscopy showed unequivocally that furin resides in the TGN where it colocalized with TGN38. In agreement with its proposed activity in multiple compartments, antibody uptake studies showed that fur/f cycles between the cell surface and TGN. Furthermore, targeting to the TGN requires sequences in the cytoplasmic tail of the enzyme. Pulse-chase and immunofluorescence analyses demonstrated that proregion removal occurs in the endoplasmic reticulum and that cleavage may be required for exist from this compartment. Finally, we show that proregion removal is necessary but not sufficient for enzyme activation.
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PMID:Intracellular trafficking and activation of the furin proprotein convertase: localization to the TGN and recycling from the cell surface. 750 80

Human yolk sacs were studied by light, transmission and scanning electron microscopy. Twelve human embryos at Carnegie stages ranging from 13 to 20 (28-49 days of gestation) were used for this research. The series of events which occur in the yolk sac wall during its period of maximum functional activity were recorded. The endodermal epithelium consisted of a single layer of columnar cells which, through cellular proliferation, formed endodermal cords which became cavitated, thereby forming endodermal vesicles. At the peak of yolk sac activity, intercellular spaces became very large and isolated individual endodermal cells. The epithelial cells were characterized by numerous microvilli on their free surface, high pinocytotic activity and by the formation of dense cisternae. Abundant intracellular vesicles fused together to empty their contents into the endodermal vesicles. The luminal surfaces of both intracellular and endodermal vesicles presented microvilli. The endodermal cells were characterized by an abundant granular endoplasmic reticulum, a well-developed Golgi apparatus, numerous mitochondria and glycogen particles. Endodermal vesicles were normally seen opening into the vitelline cavity through an endodermal orifice. The surface of the outer mesothelium was covered by numerous lengthy microvilli which were denser here than in the endodermal layer. A mucus-like material, present on the surface of the mesothelium, showed relatively few alterations during the study period. The mesothelial cells were less rich in organelles and far less active than the endodermal cells. The microanatomy of the endoderm supports the contention that its cells serve as absorptive structures as well as sites of protein synthesis during early embryonic development. Therefore, the endodermal vesicles could function as a pump regulating the fluid volume into the vitelline cavity, thereby avoiding the collapse of the organ due to the absorptive activity of the endodermal cells. Furthermore, mesothelial microvilli together with their mucous material harbor a layer of serous exudate and thus create a lubricated cushion designed to protect the thin mesothelium from frictional damage.
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PMID:The structure of the human yolk sac: a scanning and transmission electron microscopic analysis. 806 3

Brefeldin A (BFA) has been shown in in vitro studies to either collapse the Golgi into the endoplasmic reticulum (ER) or the peripheral organelles into the trans-Golgi network. Our goal was to determine the effect of BFA on intestinal lipid transport, since the Golgi is thought to play an important role in this process and simultaneously establish the effectiveness of BFA in an in vivo system. We infused rats intraduodenally with glyceryl tri-[3H]oleate at 135 mumol/h for 15 h and included BFA, 750 micrograms/h, during hours 4-7 of infusion. Mass and lipid disintegrations per minute output into the lymph fell to 9% of input rates at 8 h of infusion and returned to steady-state values at 12 h of infusion. Both chylomicron and very low-density lipoprotein output were severely affected by the BFA. Electron microscopy showed that the Golgi was collapsed into the ER. Mucosal triacylglycerol (TG) mass and disintegrations per minute were increased at 7 h of infusion in BFA infused rats vs. controls in the proximal half of the intestine. Lipid absorption, lipase activity, and mucosal TG synthesis were normal in the BFA-treated rats. We conclude that BFA works in vivo and in the intestine collapses the Golgi into the ER. As a consequence, lymphatic TG transport was severely affected.
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PMID:Effect of brefeldin A on lymphatic triacylglycerol transport in the rat. 814 3

Balb/c weanling mice were intraperitoneally inoculated with a myocarditic variant of coxsackievirus B3, with the aim of characterizing more thoroughly the features of virus-induced cell injury in pancreas and heart, as well as to compare ultrastructural alterations with histological and virological findings. During the first week post-infection (pi), all animals developed acinar pancreatitis, followed by focal myocarditis. At electron microscopy, acinar cells showed patent distortion, including marked loss of organelles and zymogen granules, together with gross dilatation of rough endoplasmic reticulum. Cardiac cells presented severe cytoskeletal changes, as myofibrillar collapse with a haphazard arrangement, concomitant with a decrease in myofibril number; besides, irregular pattern of nuclear chromatin and increased presence of swollen mitochondria were often observed. As the few initially detected lymphocytes tended to disappear in necrotic foci, there was an increase in fibroblast number concurrent with progressive scarring. Ultrastructural changes in both pancreas and heart correlated with local viral replication, suggesting that cell damage is attributable to direct viral action.
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PMID:Ultrastructural study of cell injury induced by coxsackievirus B3 in pancreatic and cardiac tissues. 820 11

Using three different trans dominant mutants of bovine ARF1 affecting GDP exchange or GTP hydrolysis we demonstrate the central role of ARF1 in controlling vesicular traffic from the endoplasmic reticulum (ER) to the Golgi apparatus and between successive Golgi compartments. Overexpression of ARF1(Q71L), a mutant likely to be restricted to the GTP-bound form, resulted in the accumulation of vesicular stomatitis virus glycoprotein in pre-Golgi intermediates, inhibited transport between successive Golgi compartments, and led to a striking association of beta-COP with pre-Golgi intermediates and the Golgi stack. In contrast, ARF1(T31N), a mutant which is likely to have a preferential affinity for GDP compared to the wild-type protein, inhibited export from the ER and triggered a brefeldin A-like phenotype, resulting in the redistribution of beta-COP from Golgi membranes to the cytosol and the collapse of the Golgi into the ER. This mutant, which may efficiently sequester an ARF-specific guanine nucleotide-exchange protein (ARF-GEF), suggests that ARF and ARF-GEF are essential for export from the ER. These results are discussed in the context of the GDP and GTP-bound forms of ARF in controlling both membrane structure and vesicular traffic through the early secretory pathway.
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PMID:Dominant inhibitory mutants of ARF1 block endoplasmic reticulum to Golgi transport and trigger disassembly of the Golgi apparatus. 828 10

Thapsigargin, previously reported to release Ca2+ from non-mitochondrial stores of different cell types, as well as nigericin, were found, when used at high concentrations, to release Ca2+ and collapse the membrane potential of Trypanosoma brucei bloodstream and procyclic trypomastigotes mitochondria in situ. At similarly high concentrations (> 10 microM), thapsigargin was also found to release Ca2+ and collapse the membrane potential of isolated rat liver mitochondria. These results indicate that care should be taken when attributing the effects of thapsigargin in intact cells to the specific inhibition of the sarcoplasmic and endoplasmic reticulum Ca(2+)-ATPase family of calcium pumps. In addition, we have found no evidence for an increase in intracellular Ca2+ by release of the ion from intracellular stores by nigericin, measuring changes in cytosolic Ca2+ by dual wavelength spectrofluorometry in fura-2-loaded T. brucei bloodstream trypomastigotes or measuring Ca2+ transport in digitonin-permeabilized cells.
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PMID:Thapsigargin causes Ca2+ release and collapse of the membrane potential of Trypanosoma brucei mitochondria in situ and of isolated rat liver mitochondria. 847 1

We have demonstrated previously that crystal violet induces a rapid, dose-related collapse of the inner mitochondrial membrane potential of Trypanosoma cruzi epimastigotes. In this work, we show that crystal violet-induced dissipation of the membrane potential was accompanied by an efflux of Ca2+ from the mitochondria. In addition, crystal violet inhibited the ATP-dependent, oligomycin-, and antimycin A-insensitive Ca2+ uptake by digitonin-permeabilized epimastigotes. Crystal violet also induced Ca2+ release from the mitochondria and endoplasmic reticulum of digitonin-permeabilized trypomastigotes. Furthermore, crystal violet inhibited Ca2+ uptake and the (Ca(2+)-Mg2+)-ATPase of a highly enriched plasma membrane fraction of epimastigotes, thus indicating an inhibition of other calcium transport mechanisms of the cells. Disruption of Ca2+ homeostasis by crystal violet may be a key process leading to trypanosome cell injury by this drug.
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PMID:Disruption of Ca2+ homeostasis in Trypanosoma cruzi by crystal violet. 850 68

Morphological changes of the smooth endoplasmic reticulum (SER) in rat cerebellar Purkinje cell dendrites were examined under apneic conditions for 1-5 minutes, induced by an incision of the diaphragm and the collapse of the lungs. The dendrites obtained from control rats contained a tubular network of the SER and hypolemmal cisterns adjacent to the plasma membrane. After a 3-5-minute apnea, the cytoplasm was occupied by many flattened cisterns stacked into lamellae, referred to as "lamellar bodies." A quantitative analysis revealed that the number of lamellar bodies became maximum after 3 minutes of apnea. After the treatment time, they increased in size by adding new cisterns to the previous core lamellae. This analysis also showed that the total amount of the SER membranes contained in a dendrite did not change during anoxia. Conformational changes from the tubular or hypolemmal SER to lamellar bodies during brief anoxia might occur through a transient and intermediate form of "fenestrated cisterns," flat across the transverse plane and penetrated by many longitudinally arranged microtubules. We suggest that these morphological changes of the SER during brief anoxia are not fixation artifacts but represent a biological reaction for protecting against intracellular abnormalities during anoxia.
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PMID:Conformational changes of smooth endoplasmic reticulum induced by brief anoxia in rat Purkinje cells. 874 25

The mechanisms that direct positive-stranded RNA virus replication complexes to plant and animal cellular membranes are poorly understood. We describe a specific interaction between a replication protein of an RNA plant virus and membranes in vitro and in live cells. The tobacco etch virus (TEV) 6 kDa protein associated with membranes as an integral protein via a central 19 amino acid hydrophobic domain. In the presence or absence of other viral proteins, fluorescent fusion proteins containing the 6 kDa protein associated with large vesicular compartments derived from the endoplasmic reticulum (ER). Infection by TEV was associated with a collapse of the ER network into a series of discrete aggregated structures. Viral RNA replication complexes from infected cells were also associated with ER-like membranes. Targeting of TEV RNA replication complexes to membranous sites of replication is proposed to involve post-translational interactions between the 6 kDa protein and the ER.
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PMID:Formation of plant RNA virus replication complexes on membranes: role of an endoplasmic reticulum-targeted viral protein. 923 14

Labial glands of the tobacco hornworm Manduca sexta (Lepidoptera: Sphingiidae, homologues of Drosophila salivary glands, undergo programmed cell death (PCD) in a 4-day period during larva-to-pupa metamorphosis. The programmed death of the labial gland was examined by electron microscopy and measurement of protein synthesis as well as measurement of DNA synthesis, end-labeling of single strand breaks, and pulsed-field gel electrophoresis. One of the earliest changes observed is a sharp drop in synthesis of most proteins, coupled with synthesis of a glycine-rich protein, reminiscent of silk-like proteins. From a morphological standpoint, during the earliest phases the most prominent changes are the formation of small autophagic vacuoles containing ribosomes and an apparent focal dissolution of the membranes of the endoplasmic reticulum, whereas later changes include differing destruction at the lumenal and basal surfaces of the cell and erosion of the basement membrane. By the fourth day of metamorphosis, individual cells become rapidly vacuolated in a cell-independent manner. In the vacuolated cells on day 3, chromatin begins to coalesce. It is at this period that unequivocal nucleosomal ladders are seen and end-labeling in situ or electrophoretic techniques document single on double-strand breaks, respectively. DNA synthesis ceases shortly after the molt to the fifth instar, as detected by incorporation of tritiated thymidine and weak TUNEL labeling. Large size fragments of DNA are seen shortly after DNA synthesis ceases and thence throughout the instor, raising the possibility of potential limitations built into the cells before their final collapse.
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PMID:Protein synthesis, DNA degradation, and morphological changes during programmed cell death in labial glands of Manduca sexta. 943 39


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