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81.
82.
Sun2 is a novel mammalian inner nuclear membrane protein 总被引:1,自引:0,他引:1
Hodzic DM Yeater DB Bengtsson L Otto H Stahl PD 《The Journal of biological chemistry》2004,279(24):25805-25812
Sun protein (Sun1 and Sun2) cDNAs were previously cloned based on the homology of their C-terminal regions (SUN (Sad1 and UNC) domain) with the Caenorhabditis elegans protein UNC-84 whose mutation disrupts nuclear migration/positioning. In this study, we raised an anti-Sun2 serum and identified Sun2 in mammalian cells. In HeLa cells, Sun2 displays a nuclear rim-like pattern typical for a nuclear envelope protein. The Sun2 antibody signal co-localizes with nuclear pore and INM markers signals. The rim-like pattern was also observed with the recombinant full-length Sun2 protein fused to either EGFP or V5 epitopes. In addition, we found that a recombinant truncated form of Sun2, extending from amino acids 26 to 339, is sufficient to specify the nuclear envelope localization. Biochemical analyses show that Sun2 is an 85-kDa protein that is partially insoluble in detergent with high salt concentration and in chaotropic agents. Furthermore, Sun2 is enriched in purified HeLa cell nuclei. Electron microscopy analysis shows that Sun2 localizes in the nuclear envelope with a sub-population present in small clusters. Additionally, we show that the SUN domain of Sun2 is localized to the periplasmic space between the inner and the outer nuclear membranes. From our data, we conclude that Sun2 is a new mammalian inner nuclear membrane protein. Because the SUN domain is conserved from fission yeast to mammals, we suggest that Sun2 belongs to a new class of nuclear envelope proteins with potential relevance to nuclear membrane function in the context of the involvement of its components in an increasing spectrum of human diseases. 相似文献
83.
MT1-MMP-dependent neovessel formation within the confines of the three-dimensional extracellular matrix 总被引:3,自引:0,他引:3
Chun TH Sabeh F Ota I Murphy H McDonagh KT Holmbeck K Birkedal-Hansen H Allen ED Weiss SJ 《The Journal of cell biology》2004,167(4):757-767
During angiogenesis, endothelial cells initiate a tissue-invasive program within an interstitial matrix comprised largely of type I collagen. Extracellular matrix-degradative enzymes, including the matrix metalloproteinases (MMPs) MMP-2 and MMP-9, are thought to play key roles in angiogenesis by binding to docking sites on the cell surface after activation by plasmin- and/or membrane-type (MT) 1-MMP-dependent processes. To identify proteinases critical to neovessel formation, an ex vivo model of angiogenesis has been established wherein tissue explants from gene-targeted mice are embedded within a three-dimensional, type I collagen matrix. Unexpectedly, neither MMP-2, MMP-9, their cognate cell-surface receptors (i.e., beta3 integrin and CD44), nor plasminogen are essential for collagenolytic activity, endothelial cell invasion, or neovessel formation. Instead, the membrane-anchored MMP, MT1-MMP, confers endothelial cells with the ability to express invasive and tubulogenic activity in a collagen-rich milieu, in vitro or in vivo, where it plays an indispensable role in driving neovessel formation. 相似文献
84.
Boldt HB Glerup S Overgaard MT Sottrup-Jensen L Oxvig C 《Protein expression and purification》2006,48(2):261-273
Although pregnancy-associated plasma protein-A (PAPP-A), a modulator of insulin-like growth factor (IGF) activity through its cleavage of IGF-binding protein (IGFBP)-4 and -5, has been known for more than two decades, knowledge about its domain architecture is still incomplete. Using position-specific iterative BLAST, we have identified distant relatives of the PAPP-A N-terminal sequence stretch of 250 residues. We present evidence that a protein domain with weak similarity to known laminin G-like (LG) modules is contained within this region, and we propose that PAPP-A and PAPP-A2 are new and unique members in the group of LG proteins as the pappalysins represent the first examples where LG modules are associated with proteinases. Fourteen beta-strands characteristic for the LG structure were tentatively located within the PAPP-A LG (PA-LG) module using secondary structure prediction and sequence alignment. Upon mammalian expression of PAPP-A truncation mutants, we defined domain boundaries showing that PA-LG is an autonomously folding unit, which spans the first 243 residues. We were unable to express PAPP-A variants which lack the PA-LG module, suggesting a possible role in stabilization of the proteolytic domain. To obtain larger amounts of protein for functional and structural analysis, the defined PA-LG domain was expressed in bacteria and folded in vitro. In addition, the availability of recombinant PA-LG module may potentially improve diagnostic assays based on the measurement of PAPP-A antigen, and also facilitate the study of PAPP-A in animal model systems. 相似文献
85.
Henning R. Gockel Johannes Schumacher Ines Gockel Hauke Lang Thomas Haaf Markus M. Nöthen 《Human genetics》2010,128(4):353-364
Despite increasing understanding of the pathophysiology of achalasia, the etiology of this esophageal motility disorder remains
largely unknown. However, the occurrence of familial achalasia and its association with well-defined genetic syndromes suggest
the involvement of genetic factors. Mutant mouse models display gastrointestinal disturbances that are similar to those observed
in achalasia patients. The candidate gene approach has revealed some promising results; however, it has not established conclusive
links to specific genes so far. The aim of this review was to summarize current knowledge of the genetics of achalasia. We
also discuss the extent to which our understanding of achalasia is likely to be enhanced through future molecular genetic
research. 相似文献
86.
In this work, an alternative to conventional preparation procedures for scanning electron microscopy (SEM) analysis of Cryptococcus neoformans was performed. The cells were fixed directly in the agar culture. This method is simpler than others already reported and the morphology of the cells was well preserved. 相似文献
87.
Environmental DNA libraries are important sources for novel biocatalyst genes but activity screening for relevant enzymes is often inefficient. Therefore, we have constructed the transposon MuExpress which randomly integrates in vitro into existing bacterial artificial chromosome (BAC) or cosmid libraries and permits the inducible expression of its flanking regions in both directions. Furthermore, this transposon allows the bidirectional sequencing of the respective clones starting from unique primer binding sites. 相似文献
88.
89.
Baratto CM Dutra V Boldo JT Leiria LB Vainstein MH Schrank A 《Current microbiology》2006,53(3):217-221
Metarhizium anisopliae infects arthropods via a combination of specialized structures and cuticle degradation. Hydrolytic enzymes are accepted as key factors for the host penetration step and include chitinases. The characterization of the chi2 chitinase gene from M. anisopliae var. anisopliae is reported. The chi2 gene is interrupted by two short introns and is 1,542-bp long, coding a predicted protein of 419 amino acids with a stretch of 19 amino acid residues displaying characteristics of signal peptide. The predicted chitinase molecular mass is 44 kDa with a mature protein of 42 kDa and a theoretical pI of 4.8. The comparison of the CHI2 predicted protein to fungal orthologues revealed similarity to the glycohydrolase family 18 and a phylogenetic analysis was conducted. The chi2 gene is up-regulated by chitin as a carbon source and in conditions of fungus autolysis, and is down-regulated by glucose. This regulation is consistent with the presence of putative CreA/Crel/Crr1 carbon catabolic repressor binding domains on the regulatory sequence. 相似文献
90.
Hsu M Muchova L Morioka I Wong RJ Schröder H Stevenson DK 《Biochemical and biophysical research communications》2006,343(3):738-744
Heme oxygenase-1 (HO-1) plays a central role in antioxidant and anti-inflammatory actions, which may be mediated through its formation of biliverdin/bilirubin and carbon monoxide. HMG-CoA reductase inhibitors (statins) induce in vitro HO-1 expression and are reported to have pleiotropic benefits that reduce oxidative stress in the vasculature. We characterized the effects of statins on in vivo HO-1 expression in various extravascular tissues: liver, lung, brain, and heart. Adult mice were orally administered simvastatin, lovastatin, atorvastatin, or rosuvastatin. HO activity significantly increased in a statin- and tissue-specific manner, with all statins increasing heart and lung activity within 24 h. Significant elevations of HO-1 protein and mRNA were also observed in heart and lung after atorvastatin treatment. We conclude that in vivo HO-1 induction is statin- and tissue-specific. Through this pathway, statins may confer antioxidant and anti-inflammatory actions in the vasculature and extravascular systems. 相似文献