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81.
82.
Calreticulin is a Ca2+-buffering ER chaperone that also modulates cell adhesiveness. In order to study the effect of calreticulin on the expression
of adhesion-related genes, we created a calreticulin inducible Human Embryonic Kidney (HEK) 293 cell line. We found that fibronectin
mRNA and both intra- and extra-cellular fibronectin protein levels increased following calreticulin induction. However, despite
this increase in fibronectin, HEK293 cells did not assemble an extracellular fibrillar fibronectin matrix regardless of the
level of calreticulin expression. Furthermore, HEK293 cells exhibited a poorly organized actin cytoskeleton, did not have
clustered fibronectin receptors at the cell surface, and did not form focal contacts. This likely accounts for the lack of
fibronectin matrix deposition by these cells regardless of calreticulin expression level. Vinculin abundance did not appreciably
increase upon calreticulin induction and the level of active c-Src, a regulatory kinase of focal contacts, was found to be
abundant and unregulated by calreticulin induction in these cells. The inability to form stable focal contacts and to commence
fibronectin fibrillogenesis due to high c-Src activity may be responsible for the poor adhesive phenotype of HEK 293 cells.
Thus, we show here that HEK293 cells are not suitable for microscopical studies of cell-substratum adhesions, but are best
suited for biochemical studies.
S. Papp and M. P. Fadel have contributed equally to this work. 相似文献
83.
Willis CK Menzies AK Boyles JG Wojciechowski MS 《Integrative and comparative biology》2011,51(3):364-373
White-nose syndrome (WNS) has caused alarming declines of North American bat populations in the 5 years since its discovery. Affected bats appear to starve during hibernation, possibly because of disruption of normal cycles of torpor and arousal. The importance of hydration state and evaporative water loss (EWL) for influencing the duration of torpor bouts in hibernating mammals recently led to "the dehydration hypothesis," that cutaneous infection of the wing membranes of bats with the fungus Geomyces destructans causes dehydration which in turn, increases arousal frequency during hibernation. This hypothesis predicts that uninfected individuals of species most susceptible to WNS, like little brown bats (Myotis lucifugus), exhibit high rates of EWL compared to less susceptible species. We tested the feasibility of this prediction using data from the literature and new data quantifying EWL in Natterer's bats (Myotis nattereri), a species that is, like other European bats, sympatric with G. destructans but does not appear to suffer significant mortality from WNS. We found that little brown bats exhibited significantly higher rates of normothermic EWL than did other bat species for which comparable EWL data are available. We also found that Natterer's bats exhibited significantly lower rates of EWL, in both wet and dry air, compared with values predicted for little brown bats exposed to identical relative humidity (RH). We used a population model to show that the increase in EWL required to cause the pattern of mortality observed for WNS-affected little brown bats was small, equivalent to a solitary bat hibernating exposed to RH of ~95%, or clusters hibernating in ~87% RH, as opposed to typical near-saturation conditions. Both of these results suggest the dehydration hypothesis is plausible and worth pursuing as a possible explanation for mortality of bats from WNS. 相似文献
84.
Hay-Koren A Caspi M Zilberberg A Rosin-Arbesfeld R 《Molecular biology of the cell》2011,22(3):399-411
Wnt/β-catenin signaling plays a central role in development and is also involved in a diverse array of diseases. β-Catenin activity is tightly regulated via a multiprotein complex that includes the kinase glycogen synthase kinase-3β (GSK-3β). GSK-3β phosphorylates β-catenin, marking it for ubiquitination and degradation via the proteasome. Thus in regulation of the Wnt pathway, the ubiquitin system is known to be involved mostly in mediating the turnover of β-catenin, resulting in reduced Wnt signaling levels. Here we report that an arm of the ubiquitin system increases β-catenin protein levels. We show that GSK-3β directly interacts with the E3 ubiquitin ligase identified by differential display (EDD) that also binds β-catenin. Expression of EDD leads to enhanced nuclear accumulation of both GSK-3β and β-catenin and results in up-regulation of β-catenin expression levels and activity. Importantly, EDD ubiquitinates β-catenin through Lys29- or Lys11-linked ubiquitin chains, leading to enhanced stability of β-catenin. Our results demonstrate a role for the ubiquitin system in up-regulation of the Wnt signaling pathway, suggesting that EDD could function as a colorectal oncogene. 相似文献
85.
Dukgyu Lee Tatsujiro Oka Beth Hunter Alison Robinson Sylvia Papp Kimitoshi Nakamura Wattamon Srisakuldee Barbara E. Nickel Peter E. Light Jason R. B. Dyck Gary D. Lopaschuk Elissavet Kardami Michal Opas Marek Michalak 《PloS one》2013,8(2)
Background
Calreticulin, a Ca2+-buffering chaperone of the endoplasmic reticulum, is highly expressed in the embryonic heart and is essential for cardiac development. After birth, the calreticulin gene is sharply down regulated in the heart, and thus, adult hearts have negligible levels of calreticulin. In this study we tested the role of calreticulin in the adult heart.Methodology/Principal Findings
We generated an inducible transgenic mouse in which calreticulin is targeted to the cardiac tissue using a Cre/loxP system and can be up-regulated in adult hearts. Echocardiography analysis of hearts from transgenic mice expressing calreticulin revealed impaired left ventricular systolic and diastolic function and impaired mitral valve function. There was altered expression of Ca2+ signaling molecules and the gap junction proteins, Connexin 43 and 45. Sarcoplasmic reticulum associated Ca2+-handling proteins (including the cardiac ryanodine receptor, sarco/endoplasmic reticulum Ca2+-ATPase, and cardiac calsequestrin) were down-regulated in the transgenic hearts with increased expression of calreticulin.Conclusions/Significance
We show that in adult heart, up-regulated expression of calreticulin induces cardiomyopathy in vivo leading to heart failure. This is due to an alternation in changes in a subset of Ca2+ handling genes, gap junction components and left ventricle remodeling. 相似文献86.
A combination of gene expression ranking and co‐expression network analysis increases discovery rate in large‐scale mutant screens for novel Arabidopsis thaliana abiotic stress genes 下载免费PDF全文
87.
Tomá? Venit Rastislav Dzijak Al?běta Kalendová Michal Kahle Jana Roho?ková Volker Schmidt Thomas Rülicke Birgit Rathkolb Wolfgang Hans Alexander Bohla Oliver Eickelberg Tobias Stoeger Eckhard Wolf Ali ?nder Yildirim Valérie Gailus-Durner Helmut Fuchs Martin Hrabě de Angelis Pavel Hozák 《PloS one》2013,8(4)
88.
William T. Starmer Michal Polak Larry L. Wolf J. S. F. Barker 《Evolution; international journal of organic evolution》1998,52(3):806-815
Quantitative genetic analysis of the ovariole number of the Australian Hibiscus flower-breeding Drosophila hibisci Bock was conducted on populations from two localities along a latitudinal cline in ovariole number previously observed in the species (Starmer et al., in press). Parental strains, F1, F1r (reciprocal), F2, backcross, and backcross reciprocal generations were used in a line-cross (generation means) analysis. This analysis revealed both additive and epistatic effects as important determinants of variation in ovariole number when larvae were reared at 25°C. Maternal effects and maternal-by-progeny genetic interactions were not significant. These results are comparable to previous studies that document epistatic components as genetic determinants of ovariole number in D. melanogaster. Parallel studies on ovariole number in D. hibisci parental and hybrid generations (F1 and F1r) reared as larvae at three temperatures (18°, 21.5°, and 25°C) showed environmental effects and genotype-by-environment interactions as significant influences on the phenotype. Maternal effects were present when temperature of larval development was considered and significant, nonlinear environmental effects were detected. Field collections of D. hibisci females showed that field conditions result in significant departure of ovariole number from comparable laboratory reared females. The significant epistatic genetic effects, genotype-by-environment interactions, and maternal effects indicate that the genetic architecture of traits, such as ovariole number, may be more complex than often acknowledged and thus may be compatible with Wright's view of a netlike relationship between the genome and complex characters (Wright 1968). 相似文献
89.
Moravec J Krystof V Hanus J Havlícek L Moravcová D Fuksová K Kuzma M Lenobel R Otyepka M Strnad M 《Bioorganic & medicinal chemistry letters》2003,13(18):2993-2996
Purine inhibitors of cyclin-dependent kinases attract attention as potential anticancer drugs because their first representative roscovitine recently entered clinical trials. Although well described in terms of structure-activity relationships, we still present here a novel modification of the purine scaffold influencing their inhibitory properties. The introduced C-8 substituents, however, lowered the CDK inhibitory activity of roscovitine, whereas the antiproliferative potential of several derivatives remained high. 相似文献
90.