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At least 523 records · Page 29Linked to original sources
PubMed2006

Endomannosidase processes oligosaccharides of alpha1-antitrypsin and its naturally occurring genetic variants in the Golgi apparatus.

Endomannosidase provides an alternate glucose-trimming pathway in the Golgi apparatus. However, it is unknown if the action of endomannosidase is dependent on the conformation of the substrate. We have investigated the processing by endomannosidase of the alpha1-antitrypsin oligosaccharides and its disease-causing misfolded Z and Hong Kong variants. Oligosaccharides of wild-type and misfolded alpha1-antitrypsin expressed in castanospermine-treated hepatocytes or glucosidase II-deficient Phar 2.7 cells were selectively processed by endomannosidase and subsequently converted to complex type oligosaccharides as indicated by Endo H resistance and PNGase F sensitivity. Overexpression of endomannosidase in castanospermine-treated hepatocytes resulted in processing of all oligosaccharides of wild-type and variants of alpha1-antitrypsin. Thus, endomannosidase does not discriminate the folding state of the substrate and provides a back-up mechanism for completion of N-glycosylation of endoplasmic reticulum-escaped glucosylated glycoproteins. For exported misfolded glycoproteins, this would provide a pathway for the formation of mature oligosaccharides important for their proper trafficking and correct functioning.

Animals↗
PubMed2000

Aggregation of ubiquitin and a mutant ALS-linked SOD1 protein correlate with disease progression and fragmentation of the Golgi apparatus.

Transgenic mice that express the G93A mutation of human Cu,Zn superoxide dismutase (SOD1(G93A)), found in familial amyotrophic lateral sclerosis (FALS), showed clinical symptoms and histopathological changes of sporadic ALS, including fragmentation of the neuronal Golgi apparatus (GA). The finding of fragmented neuronal GA in asymptomatic mice, months before the onset of paralysis, suggests that the GA is an early target of the pathological processes causing neuronal degeneration. Transgenic mice expressing human SOD1(G93A) have aggregates of mutant protein and ubiquitin in neuronal and glial cytoplasm; they appeared first in the neuropil and later in the perikarya of motor neurons, where they were adjacent to fragmented GA. The aggregates of SOD1(G93A) appeared in neuronal perikarya of asymptomatic mice containing fragmented GA. The numbers of neurons with deposits of SOD1(G93A) and fragmented GA progressively increased with age. Immuno-electron microscopy using colloidal gold showed labeling of ubiquitin and SOD1 over 13 nm thick cytoplasmic filaments. Spinal cord extracts showed a 20-fold increase of SOD1(G93A) in transgenic mice compared to the wild-type protein in controls. The results suggest a causal relationship between the aggregation of mutant SOD1 and ubiquitin, fragmentation of the Golgi apparatus of motor neurons and neurodegeneration.

Amyotrophic Lateral Sclerosis↗
PubMed1999

Fragmentation of the Golgi apparatus of Betz cells in patients with amyotrophic lateral sclerosis.

The Golgi apparatus (GA) of the large pyramidal motor neurons in the cerebral cortex (Betz cells), was examined in sixteen patients with sporadic amyotrophic lateral sclerosis (ALS), in one patient with familial ALS (FALS), and in ten non-ALS age matched controls including one patient with Huntington's disease and one patient with a brain infarct. The GA was immunostained with an antibody against the MG-160 protein, a conserved sialoglycoprotein of the medial cisternae of the organelle. In ALS, 13.2% of counted Betz cells had fragmented GA in contrast to 0.6% in the ten non-ALS controls. The fragmentation of the GA of Betz cells was identical to that previously reported in spinal cord motor neurons from patients with sporadic ALS and in transgenic mice expressing the G93A mutation of the gene encoding the Cu/Zn superoxide dismutase. The striking morphological similarity between the fragmentation of the GA observed in Betz cells and in spinal cord motor neurons suggests that a similar pathogenic mechanism is responsible for both, and that the fragmentation of the GA of the spinal cord motor neurons is not a consequence of deafferentation due to the degeneration of the Betz cells.

Adult↗
PubMed1998

1898: the Golgi apparatus emerges from nerve cells.

A century ago, Camillo Golgi discovered in neurons an intracellular network of anastomosing threads, impregnated by the chromoargentic reaction he had devised to stain the nervous tissue. This structure, designated by Golgi as 'internal reticular apparatus', was soon detected in a wide variety of eukaryotic cells. However, skepticism arose on the existence of the Golgi apparatus in the first decades of this century, when it was fiercely debated whether this structure represented a genuine new cell constituent or an artifact due to the deposit of metallic impregnation on diverse cytoplasmic structures. The reality of the Golgi apparatus became established unequivocally only with the application of electron microscopy; with the visualization of its fine structure, the apparatus finally achieved the status of cytoplasmic organelle, and thus, linked with Golgi's name, entered the modern era of investigation on its components, chemistry and function.

Animals↗
PubMed1984

Associations of elements of the Golgi apparatus with microtubules.

The intracellular spatial relationships between elements of the Golgi apparatus (GA) and microtubules in interphase cells have been explored by double immunofluorescence microscopy. By using cultured cells infected with the temperature-sensitive Orsay-45 mutant of vesicular stomatitis virus and a temperature shift-down protocol, we visualized functional elements of the GA by immunolabeling of the G protein of the virus that was arrested in the GA during its intracellular passage to the plasma membrane 13 min after the temperature shift-down. Complete disassembly of the cytoplasmic microtubules by nocodazole at the nonpermissive temperature before the temperature shift led to the dispersal of the GA elements, from their normal compact perinuclear configuration close to the microtubule-organizing center (MTOC) into the cell periphery. Washout of the nocodazole that led to the reassembly of the microtubules from the MTOC also led to the recompaction of the GA elements to their normal configuration. During this recompaction process, GA elements were seen in close lateral apposition to microtubules. In cells treated with nocodazole followed by taxol, an MTOC developed, but most of the microtubules were free of the MTOC and were assembled into bundles in the cell periphery. Under these circumstances, the GA elements that had been dispersed into the cell periphery by the nocodazole treatment remained dispersed despite the presence of an MTOC. In cells treated directly with taxol, free microtubules were seen in the cytoplasm in widely different, bundled configurations from one cell to another, but, in each case, elements of the GA appeared to be associated with one of the two end regions of the microtubule bundles, and to be uncorrelated with the locations of the vimentin intermediate filaments in these cells. These results are interpreted to suggest two types of associations of elements of the GA with microtubules: one lateral, and the other (more stable) end-on. The end-on association is suggested to involve the minus-end regions of microtubules, and it is proposed that this accounts for the GA-MTOC association in normal cells.

Animals↗
PubMed1987

Arrest of proteolipid transport through the Golgi apparatus in Jimpy brain.

Immunocytochemical investigations were performed on Jimpy and control mouse brains using three specific anti-myelin proteolipids antisera: immunoaffinity purified multivalent anti-(PLP + DM-20) proteolipid antibodies, anti-C-terminal hexapeptide 271-276 and anti-tridecapeptide 117-129 antisera. The results show that oligodendrocytes and myelin sheaths in normal mouse brain are labelled to the same extent by the three specific antisera; in contrast, in Jimpy brain these cellular structures are only stained by the multivalent antibodies and the site-specific, anti-tridecapeptide antiserum. The absence of labelling with C-terminal hexapeptide antiserum in mutant brain is interpreted as the result of either a large deletion or a point mutation producing a frameshift in the C-terminal part of the sequences of the proteolipids PLP and DM-20. Furthermore, we show that this mutation prevents the normal transport of proteolipid molecules through the Golgi apparatus. The existence of a minor, extra-Golgi apparatus metabolic route for proteolipids to myelin structures is also discussed.

Animals↗
PubMed1989

Lectin-gold cytochemistry of the Golgi apparatus in rabbit luteal cells, with special emphasis on the formation of a lysosomal-type membrane.

In rabbit luteal cells embedded in glycolmethacrylate and stained with PTA at low pH highly glycosylated membrane patches can be observed after vesiculation of the trans-Golgi network. As these membranes could be prelysosomal, their sialic acid content was investigated by post-embedding labeling with Limax flavus agglutinin (LFA)/fetuin-Au. Additional labeling of the Golgi apparatus was performed with Wheat germ agglutinin (WGA)/ovomucoid Au, Ricinus communis agglutininI (RCAI)/Au and Helix pomatia agglutinin (HPA)/Au. The sections were then counterstained with PTA at low pH, which allows a clear distinction between the elements of the trans-Golgi network (G2-G1) and the saccules of the stack (g). With WGA, LFA and RCAI the trans-Golgi network was observed to be clearly more reactive than the stack. After vesiculation most intense labeling was found over the highly glycosylated vacuolar membranes derived from the G2-element. The limiting membrane of lysosomes, the MvB's and the plasma membrane also reacted strongly. Colloidal gold particles were also found over the membranes of the vacuoles derived from G1. The Golgi stack showed a lower reactivity and label for all three lectins could be found over three to four saccules of the stack (g3-g4). The matrix of the lysosomes was slightly labeled. Labeling with HPA was absent from the trans saccules and was consistently found in the cis and cis-most (g4-g5) saccules of the stack. Some cytoplasmic vesicles near the cell border were also labeled. With our procedure the Golgi apparatus can easily be detected and it is apparent that in rabbit luteal cells the highest lectin reactivity is found in the trans-Golgi network.(ABSTRACT TRUNCATED AT 250 WORDS)

Agglutinins↗
PubMed1994

Inhibition of protein synthesis disrupts the Golgi apparatus in the fission yeast, Schizosaccharomyces pombe.

Schizosaccharomyces pombe was treated with either cycloheximide or anisomycin at levels sufficient to inhibit > 95% of protein synthesis for periods upon to 3 h, equivalent to one cell cycle. Treatment for as little as 1 h caused significant loss of the Golgi apparatus by both immunofluorescence and electron microscopy. The loss was quantitated by stereology on electron micrographs. Nearly 90% of the stacked Golgi was lost over a 3 h period. No other intracellular membrane compartment seemed to be affected. Measurement of enzyme activities confirmed these observations. The activity of a resident of the Golgi apparatus, alpha-1,2 galactosyltransferase, was reduced over this time, whereas the endoplasmic reticulum marker, BiP, and the cytoplasmic enzyme, hexokinase, were unaffected. The morphological changes associated with cycloheximide addition were reversed on its removal, though there was a lag before cells recommenced growth or secretion of the enzyme, acid phosphatase.

Acid Phosphatase↗
PubMed1988

Wheat germ agglutinin fracture-label of Golgi apparatus membranes in proliferating cells.

The thin section fracture-label technique has been recently used to analyze the distribution and compartmentalization of fully glycosylated components on intracellular membranes. Labelling with the lectin wheat germ agglutinin over the freeze-fractured membranes of Golgi apparatus in various secretory and non-secretory cells as well as in human peripheral lymphocytes was always very weak or absent even over the trans-most cisternae. In order to investigate if the labelling density may reflect the cellular activity in membrane biogenesis, we used in this study wheat germ agglutinin fracture-label of rapidly proliferating cells and mitogen-activated lymphocytes. Labelling over the fractured cisternae of the medial and trans portions of the Golgi apparatus was intense. Treatment with cycloheximide of proliferating cells induced a drastic reduction of the labelling over the Golgi cisternae.

Cell Division↗
PubMed1993

Properties of [Ca2+ + Mg2+]-adenosine triphosphatases in the Golgi apparatus and microsomes of the lactating mammary glands of cows.

The [Ca2+ + Mg2+]-ATPase activity of bovine lactating mammary gland is associated with membranes. This study compares the ATPase activity in microsomal membranes to that of the Golgi apparatus. The enzyme activity in both fractions hydrolyzed Ca(2+)-ATP and Mg(2+)-ATP. The ATPase activities were inhibited by p-chloromercuribenzoate, indicating the involvement of a sulfhydryl group for activity. Although calmodulin had no effect on the ATPase activities of the two fractions, calmodulin antagonists (chlorpromazine, fluphenazine, and trifluoperazine) were inhibitory. Strong inhibitors of the ATPase activities were vanadate, dicyclohexyl-carbodiimide, La3+, and Zn2+. There were some differences in the activities from two membrane fractions. Although both fractions could hydrolyze all of the triphosphonucleotides, cytidine-5'-triphosphate and uridine-5'-triphosphate were poor substrates for the Golgi enzyme. Detergents diminished the activity of the microsomal enzyme to a much greater extent than the ATPase of the Golgi apparatus. Thus, the intact membrane may be more critical to microsomal activity. The role of these enzymes in Ca2+ accumulation in milk is discussed.

Animals↗
PubMed1985

Carbon tetrachloride-induced inhibition of hepatocyte lipoprotein secretion: functional impairment of Golgi apparatus in the early phases of such injury.

Functional change of liver Golgi apparatus during carbon tetrachloride (CCl4) poisoning was demonstrated both in rat isolated hepatocytes and in the whole animal. The "in vitro" experimental model provided evidence of Golgi derangement early after giving the haloalkane. The "in vivo" analyses also showed that such an alteration involves both formative and secretory sides of the subcellular structure.

Animals↗
PubMed1976

Similarities of the Golgi apparatus membrane and the plasma membrane in rat liver cells.

A Golgi apparatus-rich fraction and a plasma membrane-rich fraction were isolated from a common homogenate of rat liver. Their respective buovant densities, appearances in the electron microscope and 5'-nucleotidase and UDP-galactose ovalbumin galactosyltransferase activities were in accord with published data on separately isolated Golgi apparatus-rich and plasma membrane-rich fractions. Contamination by endoplasmic reticulum and mitochondria was low. Gel electrophoresis of the membrane proteins of the Golgi apparatus-rich and plasma membrane-rich fractions (separately and mixed) showed a close similarity. After Neville's demonstration that electrophoretic patterns of membrane protein subunits from different subcellular fractions are easily distinguishable, the present work demonstrates an unusually close relationship between the Golgi apparatus membrane and the cell membrane. It is possible that membrane similarity may be mediated by the transfer of membrane-bound vesicles from the Golgi apparatus to the cell membrane.

Animals↗
PubMed1977

Localization of some glycolipid glycosylating enzymes in the Golgi apparatus of rat kidney.

Cell fractions from rat kidney were isolated and studied for their ability to synthesize several possible intermediates in the biosynthesis of sulfatides and gangliosides. The enzymes studied include UDP-Gal:ceramide galactosyltransferase, UDP-Gal:glucosylceramide galactosyltransferase, UDP-Gal:galactosylceramide galactosyltransferase, and CMP-NAN:lactosylceramide sialytransferase activities. The initial glycosylation of ceramide was found to be present in all of the kidney cell fractions studied. The remaining glycosylating enzymes were largely localized in the Golgi apparatus of kidney. Thus, in addition to modifying glycoproteins for secretion, the Golgi apparatus in kidney is involved in the modification of a number of glycolipids which are destined to form cell membrane components.

Animals↗
PubMed1998

A 21-kDa polypeptide belonging to a new family of proteins is expressed in the Golgi apparatus of neural and germ cells.

We have isolated a full-length murine clone corresponding to the rat neuronal p1A75 partial cDNA (Sutcliffe, J. G., Milner, R. J., Shinnick, T. M., and Bloom, F. E. (1983) Cell 33, 671-682). It encodes a 185-residue polypeptide that displays 56% identity with p19, a protein selectively expressed in the Golgi apparatus of neural cells (Sabéran-Djoneidi, D., Marey-Semper, I., Picart, R., Studler, J.-M., Tougard, C., Glowinski, J., and Lévi-Strauss, M. (1995) J. Biol. Chem. 270, 1888-1893). An antibody directed against the recombinant polypeptide allowed us to demonstrate the existence of the natural 21-kDa protein (p21) in brain and its prominent juxtanuclear Golgi-like localization in cultured neurons. Ultrastructural observation of cultured neurons and analysis of transfected COS cells revealed a specific labeling of the Golgi apparatus, suggesting, as for p19, the presence of a Golgi targeting signal in its primary sequence. Surprisingly, p21, which is much more strongly expressed in the olfactory epithelium than p19, is also present in the Golgi complex of spermatocytes and in the flagellar middle piece of late spermatids.

Amino Acid Sequence↗
PubMed1989

Conversion of a Golgi apparatus sialyltransferase to a secretory protein by replacement of the NH2-terminal signal anchor with a signal peptide.

The beta-galactoside alpha 2,6 sialyltransferase, an integral membrane protein localized to the trans-region of the Golgi apparatus, has been converted into a catalytically active secreted protein by the replacement of the NH2-terminal signal-anchor domain with the cleavable signal peptide of human gamma-interferon. Pulse-chase analysis of the wild type and recombinant proteins expressed in stably transfected Chinese hamster ovary cells showed that the wild type sialyltransferase (47 kDa) remained cell-associated. In contrast, the signal peptide-sialyltransferase fusion protein yielded an enzymatically active 41-kDa polypeptide which was secreted with a half-time of 2-3 h, consistent with cleavage of the signal peptide. The data indicate that the catalytic domain does not contain sufficient information for retention in the Golgi apparatus and that retention signals are likely to be found in the NH2-terminal 57 amino acids of the wild type enzyme.

Animals↗
PubMed2003

"Slip, sliding away": phospholipase D and the Golgi apparatus.

Phospholipase D enzymes (PLDs) constitute a family of phosphodiesterases that catalyze the hydrolysis of phosphatidylcholine (PtdCho) to generate choline and phosphatidic acid (PtdOH), a potent lipid signaling molecule implicated in numerous physiological processes. Mammalian PLDs have been localized to multiple organelles, including the nucleus, Golgi apparatus, lysosomes, secretory granules and plasma membrane. However, the detailed mechanisms that govern targeting of PLDs to different organelles, how their local activity is controlled or indeed the nature of PA effectors are not well understood. Here, we discuss recent observations on PLD localization to the Golgi apparatus and how members of this enzyme family might play a role in regulating the structure of this organelle.

Animals↗
PubMed1984

Presence of an osmiophilic feltwork distinct from the Golgi apparatus in spinal ganglion cells of the rat.

Rat dorsal root ganglia were osmicated for 48 h at 42 degrees C in a 2% unbuffered aqueous solution of osmium tetroxide. In addition to the osmiophilic cis-element of the Golgi apparatus, the osmium stained a cytoplasmic structure which, although present in the perikaryon of all ganglionic neurons, was well developed in type B1 cells. In photographic stereopairs of 1-2 microns thick sections examined with the electron microscope at 100 kV, these osmiophilic elements appeared as long, wavy thread-like elements with fusiform enlargements. Their average diameter was smaller than that of the thinner cisternae of the smooth endoplasmic reticulum. Occasionally branched, these osmiophilic structures were oriented in all directions of space. When examined in 1.5-7 microns thick sections with a high voltage electron microscope, they formed an osmiophilic feltwork which extended from the juxtanuclear to the subplasmalemmal regions of the perikaryon. It was not connected with the osmiophilic cis-element of the Golgi apparatus. In sections of glutaraldehyde-fixed tissues impregnated with the double impregnation technique or postfixed with reduced osmium, the osmiophilic tubules were clearly distinguished from microtubules, cisternae of endoplasmic reticulum or endocytic structures.

Animals↗
PubMed2002

Molecular and phenotypic analysis of CaVRG4, encoding an essential Golgi apparatus GDP-mannose transporter.

Cell surface mannan is implicated in almost every aspect of pathogenicity of Candida albicans. In Saccharomyces cerevisiae, the Vrg4 protein acts as a master regulator of mannan synthesis through its role in substrate provision. The substrate for mannosylation of proteins and lipids in the Golgi apparatus is GDP-mannose, whose lumenal transport is catalyzed by Vrg4p. This nucleotide sugar is synthesized in the cytoplasm by pathways that are highly conserved in all eukaryotes, but its lumenal transport (and hence Golgi apparatus-specific mannosylation) is a fungus-specific process. To begin to study the role of Golgi mannosylation in C. albicans, we isolated the CaVRG4 gene and analyzed the effects of loss of its function. CaVRG4 encodes a functional homologue of the S. cerevisiae GDP-mannose transporter. CaVrg4p localized to punctate spots within the cytoplasm of C. albicans in a pattern reminiscent of localization of Vrg4p in the Golgi apparatus in S. cerevisiae. Like partial loss of ScVRG4 function, partial loss of CaVRG4 function resulted in mannosylation defects, which in turn led to a number of cell wall-associated phenotypes. While heterozygotes displayed no growth phenotypes, a hemizygous strain, containing a single copy of CaVRG4 under control of the methionine-repressible MET3 promoter, did not grow in the presence of methionine and cysteine, demonstrating that CaVRG4 is essential for viability. Mutant Candida vrg4 strains were defective in hyphal formation but exhibited a constitutive polarized mode of pseudohyphal growth. Because the VRG4 gene is essential for yeast viability but does not have a mammalian homologue, it is a particularly attractive target for development of antifungal therapies.

Amino Acid Sequence↗