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41.
Christine Kienzle Stephan A. Eisler Julien Villeneuve Tilman Brummer Monilola A. Olayioye Angelika Hausser 《Molecular biology of the cell》2013,24(3):222-233
Before entering mitosis, the stacks of the Golgi cisternae are separated from each other, and inhibiting this process delays entry of mammalian cells into mitosis. Protein kinase D (PKD) is known to be involved in Golgi-to–cell surface transport by controlling the biogenesis of specific transport carriers. Here we show that depletion of PKD1 and PKD2 proteins from HeLa cells by small interfering RNA leads to the accumulation of cells in the G2 phase of the cell cycle and prevents cells from entering mitosis. We further provide evidence that inhibition of PKD blocks mitotic Raf-1 and mitogen-activated protein kinase kinase (MEK) activation, and, as a consequence, mitotic Golgi fragmentation, which could be rescued by expression of active MEK1. Finally, Golgi fluorescence recovery after photobleaching analyses demonstrate that PKD is crucial for the cleavage of the noncompact zones of Golgi membranes in G2 phase. Our findings suggest that PKD controls interstack Golgi connections in a Raf-1/MEK1–dependent manner, a process required for entry of the cells into mitosis. 相似文献
42.
Organic Solar Cells: Following the Morphology Formation In Situ in Printed Active Layers for Organic Solar Cells (Adv. Energy Mater. 1/2016) 下载免费PDF全文
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45.
Olga Dolnik Larissa Kolesnikova Sonja Welsch Thomas Strecker Gordian Schudt Stephan Becker 《PLoS pathogens》2014,10(10)
Endosomal sorting complex required for transport (ESCRT) machinery supports the efficient budding of Marburg virus (MARV) and many other enveloped viruses. Interaction between components of the ESCRT machinery and viral proteins is predominantly mediated by short tetrapeptide motifs, known as late domains. MARV contains late domain motifs in the matrix protein VP40 and in the genome-encapsidating nucleoprotein (NP). The PSAP late domain motif of NP recruits the ESCRT-I protein tumor susceptibility gene 101 (Tsg101). Here, we generated a recombinant MARV encoding NP with a mutated PSAP late domain (rMARVPSAPmut). rMARVPSAPmut was attenuated by up to one log compared with recombinant wild-type MARV (rMARVwt), formed smaller plaques and exhibited delayed virus release. Nucleocapsids in rMARVPSAPmut-infected cells were more densely packed inside viral inclusions and more abundant in the cytoplasm than in rMARVwt-infected cells. A similar phenotype was detected when MARV-infected cells were depleted of Tsg101. Live-cell imaging analyses revealed that Tsg101 accumulated in inclusions of rMARVwt-infected cells and was co-transported together with nucleocapsids. In contrast, rMARVPSAPmut nucleocapsids did not display co-localization with Tsg101, had significantly shorter transport trajectories, and migration close to the plasma membrane was severely impaired, resulting in reduced recruitment into filopodia, the major budding sites of MARV. We further show that the Tsg101 interacting protein IQGAP1, an actin cytoskeleton regulator, was recruited into inclusions and to individual nucleocapsids together with Tsg101. Moreover, IQGAP1 was detected in a contrail-like structure at the rear end of migrating nucleocapsids. Down regulation of IQGAP1 impaired release of MARV. These results indicate that the PSAP motif in NP, which enables binding to Tsg101, is important for the efficient actin-dependent transport of nucleocapsids to the sites of budding. Thus, the interaction between NP and Tsg101 supports several steps of MARV assembly before virus fission. 相似文献
46.
Nicolas Bloemeke Kevin MeighenBerger Manuel Hitzenberger Nina C Bach Marina Parr Joao PL Coelho Dmitrij Frishman Martin Zacharias Stephan A Sieber Matthias J Feige 《The EMBO journal》2022,41(24)
One‐third of the human proteome is comprised of membrane proteins, which are particularly vulnerable to misfolding and often require folding assistance by molecular chaperones. Calnexin (CNX), which engages client proteins via its sugar‐binding lectin domain, is one of the most abundant ER chaperones, and plays an important role in membrane protein biogenesis. Based on mass spectrometric analyses, we here show that calnexin interacts with a large number of nonglycosylated membrane proteins, indicative of additional nonlectin binding modes. We find that calnexin preferentially bind misfolded membrane proteins and that it uses its single transmembrane domain (TMD) for client recognition. Combining experimental and computational approaches, we systematically dissect signatures for intramembrane client recognition by calnexin, and identify sequence motifs within the calnexin TMD region that mediate client binding. Building on this, we show that intramembrane client binding potentiates the chaperone functions of calnexin. Together, these data reveal a widespread role of calnexin client recognition in the lipid bilayer, which synergizes with its established lectin‐based substrate binding. Molecular chaperones thus can combine different interaction modes to support the biogenesis of the diverse eukaryotic membrane proteome. 相似文献
47.
Dumitrescu D Oudiz RJ Karpouzas G Hovanesyan A Jayasinghe A Hansen JE Rosenkranz S Wasserman K 《PloS one》2010,5(12):e14293
Background
Patients with systemic sclerosis (SSc) may develop exercise intolerance due to musculoskeletal involvement, restrictive lung disease, left ventricular dysfunction, or pulmonary vasculopathy (PV). The latter is particularly important since it may lead to lethal pulmonary arterial hypertension (PAH). We hypothesized that abnormalities during cardiopulmonary exercise testing (CPET) in patients with SSc can identify PV leading to overt PAH.Methods
Thirty SSc patients from the Harbor-UCLA Rheumatology clinic, not clinically suspected of having significant pulmonary vascular disease, were referred for this prospective study. Resting pulmonary function and exercise gas exchange were assessed, including peakVO2, anaerobic threshold (AT), heart rate- VO2 relationship (O2-pulse), exercise breathing reserve and parameters of ventilation-perfusion mismatching, as evidenced by elevated ventilatory equivalent for CO2 (VE/VCO2) and reduced end-tidal pCO2 (PETCO2) at the AT.Results
Gas exchange patterns were abnormal in 16 pts with specific cardiopulmonary disease physiology: Eleven patients had findings consistent with PV, while five had findings consistent with left-ventricular dysfunction (LVD). Although both groups had low peak VO2 and AT, a higher VE/VCO2 at AT and decreasing PETCO2 during early exercise distinguished PV from LVD.Conclusions
Previously undiagnosed exercise impairments due to LVD or PV were common in our SSc patients. Cardiopulmonary exercise testing may help to differentiate and detect these disorders early in patients with SSc. 相似文献48.
49.
Hellmuth A. Meyer Tobias Endermann Carsten Stephan Mette Stoedter Thomas Behrends Ingmar Wolff Klaus Jung Lutz Schomburg 《PloS one》2012,7(10)
Selenium (Se) is an essential trace element for selenoprotein biosynthesis. Selenoproteins have been implicated in cancer risk and tumor development. Selenoprotein P (SePP) serves as the major Se transport protein in blood and as reliable biomarker of Se status in marginally supplied individuals. Among the different malignancies, renal cancer is characterized by a high mortality rate. In this study, we aimed to analyze the Se status in renal cell cancer (RCC) patients and whether it correlates to cancer-specific mortality. To this end, serum samples of RCC patients (n = 41) and controls (n = 21) were retrospectively analyzed. Serum Se and SePP concentrations were measured by X-ray fluorescence and an immunoassay, respectively. Clinical and survival data were compared to serum Se and SePP concentrations as markers of Se status by receiver operating characteristic (ROC) curve and Kaplan-Meier and Cox regression analyses. In our patients, higher tumor grade and tumor stage at diagnosis correlated to lower SePP and Se concentrations. Kaplan-Meier analyses indicated that low Se status at diagnosis (SePP<2.4 mg/l, bottom tertile of patient group) was associated with a poor 5-year survival rate of 20% only. We conclude that SePP and Se concentrations are of prognostic value in RCC and may serve as additional diagnostic biomarkers identifying a Se deficit in kidney cancer patients potentially affecting therapy regimen. As poor Se status was indicative of high mortality odds, we speculate that an adjuvant Se supplementation of Se-deficient RCC patients might be beneficial in order to stabilize their selenoprotein expression hopefully prolonging their survival. However, this assumption needs to be rigorously tested in prospective clinical trials. 相似文献
50.
Grande Karen D.; Bender Michael L.; Irwin Brian; Platt Trevor 《Journal of plankton research》1991,13(1):1-16
In vitrorates of gross and net oxygen production were measuredas a function of light intensity in some plankton communitiescollected from Bedford Basin, Nova Scotia, and in a monoclonalculture of Synechococcus. The rate of gross oxygen productionwas measured by a technique in which the stable oxygen isotope,18O, serves as a photosynthetic tracer Net oxygen productionwas measured by automated Winkler technique. The rate of communityrespiration in the light was then determined by the differencebetween gross and net rates of oxygen production. In the naturalpopulations examined, neither gross nor net oxygen productionrates were significantly inhibited at the highest light intensitymeasured (500800 µE m2 s1) In a samplein which the dark respiration rate was small relative to themaximal rate of production [Pmax;sensu Platt et al (1980) JMar. Res., 38, 687701] the rates of lightrespiration were 3 times greater. In two other communities,with high rates of dark respiration relative to Pmaxthe ratesof light respiration were closer to rates of darkrespiration. In the Synechococcus clone, both gross and netoxygen production rates were inhibited at high light intensities.Rates of light respiration were found to varyas a function of light intensity. The greatest rates of respirationwere measured in samples incubated at light intensities thatwere just saturating (100 µE m2 s1). Therates of 14C production were also measured as a function oflight intensity The photosynthetic quotients, based on 14C productionrates and gross oxygen production rates, average 1 9 相似文献