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1.
J Kooy B H Toh J M Pettitt R Erlich P A Gleeson 《The Journal of biological chemistry》1992,267(28):20255-20263
We have used a serum from a patient with Sj?gren's syndrome containing high titer (100,000) anti-Golgi autoantibodies and lower titer (20,000) anti-nuclear autoantibodies to characterize the Golgi complex. The Sj?gren's syndrome serum immunoprecipitated a number of components of molecular mass 35-230 kDa from detergent extracts of [35S]methionine-labeled HeLa cells; at high dilution, the serum precipitated one major 230-kDa component. Using the Sj?gren's syndrome serum, cDNA clones encoding the Golgi autoantigen were isolated from a lambda gt11 HeLa cell cDNA library. Autoantibodies from the Sj?gren's syndrome serum, affinity purified from a recombinant bacterial fusion protein generated from one of the cDNA clones, showed Golgi staining of human, mouse, and chicken cells by immunofluorescence. The purified autoantibodies immunoprecipitated and immunoblotted a 230-kDa component. A rabbit antiserum raised to the recombinant fusion protein specifically stained the Golgi complex by immunofluorescence and reacted with a 230-kDa protein by immunoprecipitation and immunoblotting. The 230-kDa protein was recovered in both the 100,000 x g sedimentable and soluble fractions in cell lysates and in the aqueous phase of Triton X-114 extracts. The 230-kDa autoantigen was dissociated from the Golgi complex by 15-min brefeldin A treatment, dissociation kinetics similar to that of mannosidase II. However, unlike mannosidase II, autoantigen staining was markedly reduced after drug treatment. Removal of brefeldin A resulted in reassociation of the autoantigen with the Golgi complex. The epitopes recognized by the affinity purified human and rabbit antibodies were ultrastructurally localized to the cytosolic face of one side of the Golgi stack, probably the trans-face. Taken together, the 230-kDa protein is a conserved, peripheral membrane component specifically associated with one Golgi compartment. We suggest that this peripheral Golgi protein may have a role in the compartment-specific structural organization of the Golgi or in sorting and transport of proteins. 相似文献
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Dopamine modulates the plasticity of mechanosensory responses in Caenorhabditis elegans 总被引:4,自引:0,他引:4
Sanyal S Wintle RF Kindt KS Nuttley WM Arvan R Fitzmaurice P Bigras E Merz DC Hébert TE van der Kooy D Schafer WR Culotti JG Van Tol HH 《The EMBO journal》2004,23(2):473-482
Dopamine-modulated behaviors, including information processing and reward, are subject to behavioral plasticity. Disruption of these behaviors is thought to support drug addictions and psychoses. The plasticity of dopamine-mediated behaviors, for example, habituation and sensitization, are not well understood at the molecular level. We show that in the nematode Caenorhabditis elegans, a D1-like dopamine receptor gene (dop-1) modulates the plasticity of mechanosensory behaviors in which dopamine had not been implicated previously. A mutant of dop-1 displayed faster habituation to nonlocalized mechanical stimulation. This phenotype was rescued by the introduction of a wild-type copy of the gene. The dop-1 gene is expressed in mechanosensory neurons, particularly the ALM and PLM neurons. Selective expression of the dop-1 gene in mechanosensory neurons using the mec-7 promoter rescues the mechanosensory deficit in dop-1 mutant animals. The tyrosine hydroxylase-deficient C. elegans mutant (cat-2) also displays these specific behavioral deficits. These observations provide genetic evidence that dopamine signaling modulates behavioral plasticity in C. elegans. 相似文献
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Manipulations of context can affect learning and memory performance across species in many associative learning paradigms. Using taste cues to create distinct contexts for olfactory adaptation assays in the nematode Caenorhabditis elegans, we now show that performance in this associative learning paradigm is sensitive to context manipulations, and we investigate the mechanism(s) used for the integration of context cues in learning. One possibility is that the taste and olfactory stimuli are perceived as a combined, blended cue that the animals then associate with the unconditioned stimulus (US) in the same manner as with any other unitary conditioned stimuli (CS). Alternatively, an occasion-setting model suggests that the taste cues only define the appropriate context for olfactory memory retrieval without directly entering into the primary association. Analysis of genetic mutants demonstrated that the olfactory and context cues are sensed by distinct primary sensory neurons and that the animals' ability to use taste cues to modulate olfactory learning is independent from their ability to utilize these same taste cues for adaptation. We interpret these results as evidence for the occasion-setting mechanism in which context cues modulate primary Pavlovian association by functioning in a hierarchical manner to define the appropriate setting for memory recall. 相似文献
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Ten years after the identification of the gene responsible for fragile X syndrome, recent studies have revealed a list of mRNAs bound by the fragile X gene product and have identified specific sequences required for the interaction between the fragile X protein and its targets. These results are a breakthrough in understanding why absence of the fragile X protein leads to mental retardation. 相似文献
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Mahapatra A Mativandlela SP Binneman B Fourie PB Hamilton CJ Meyer JJ van der Kooy F Houghton P Lall N 《Bioorganic & medicinal chemistry》2007,15(24):7638-7646
The naphthoquinone 7-methyljuglone (5-hydroxy-7-methyl-1,4-naphthoquinone) has previously been isolated and identified as an active component of root extracts of Euclea natalensis which displays antitubercular activity. Herein, a series of synthetic and plant-derived naphthoquinone derivates of the 7-methyljuglone scaffold have been prepared and evaluated for antibacterial activity against Mycobacterium tuberculosis. Several of these compounds have been shown to operate as subversive substrates with mycothiol disulfide reductase. The absence of a direct correlation between antitubercular activity and subversive substrate efficiency with mycothiol disulfide reductase, might be a consequence of their non-specific reactivity with multiple biological targets (e.g. other disulfide reductases). 相似文献
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Joana RF Abreu Daphne de Launay Marjolein E Sanders Aleksander M Grabiec G Marleen van de Sande Paul P Tak Kris A Reedquist 《Arthritis research & therapy》2009,11(4):R121-13
Introduction
Fibroblast-like synoviocytes (FLS) from rheumatoid arthritis (RA) patients share many similarities with transformed cancer cells, including spontaneous production of matrix metalloproteinases (MMPs). Altered or chronic activation of proto-oncogenic Ras family GTPases is thought to contribute to inflammation and joint destruction in RA, and abrogation of Ras family signaling is therapeutic in animal models of RA. Recently, expression and post-translational modification of Ras guanine nucleotide releasing factor 1 (RasGRF1) was found to contribute to spontaneous MMP production in melanoma cancer cells. Here, we examine the potential relationship between RasGRF1 expression and MMP production in RA, reactive arthritis, and inflammatory osteoarthritis synovial tissue and FLS. 相似文献9.
Histopathological effects of cisplatin,doxorubicin and 5-flurouracil (5-FU) on the liver of male albino rats 下载免费PDF全文
Hassan I El-Sayyad Mohamed F Ismail F M Shalaby RF Abou-El-Magd Rajiv L Gaur Augusta Fernando Madhwa HG Raj Allal Ouhtit 《International journal of biological sciences》2009,5(5):466-473
Cisplatin, doxorubicin and fluorouracil (5-FU), drugs belonging to different chemical classes, have been extensively used for chemotherapy of various cancers. Despite extensive investigations into their hepatotoxicity, there is very limited information on their effects on the structure and ultra-structure of liver cells in vivo. Here, we demonstrate for the first time, the effects of these three anticancer drugs on rat liver toxicity using both light and electron microscopy. Light microscopic observations revealed that higher doses of cisplatin and doxorubicin caused massive hepatotoxicity compared to 5-FU treatment, including dissolution of hepatic cords, focal inflammation and necrotic tissues. Interestingly, low doses also exhibited abnormal changes, including periportal fibrosis, degeneration of hepatic cords and increased apoptosis. These changes were confirmed at ultrastructural level, including vesiculated rough endoplasmic reticulum and atrophied mitochondria with ill-differentiated cisternae, dense collection of macrophages and lymphocytes as well as fibrocytes with collagenous fibrils manifesting early sign of fibrosis, especially in response to cisplatin and doxorubicin -treatment. Our results provide in vivo evidence, at ultrastructural level, of direct hepatotoxicity caused by cisplatin, doxorubicin and 5-FU at both light and electron microscopi. These results can guide the design of appropriate treatment regimen to reduce the hepatotoxic effects of these anticancer drugs. 相似文献
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