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1.
Identification of different roles for RanGDP and RanGTP in nuclear protein import. 总被引:40,自引:9,他引:31
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The importin-alpha/beta heterodimer and the GTPase Ran play key roles in nuclear protein import. Importin binds the nuclear localization signal (NLS). Translocation of the resulting import ligand complex through the nuclear pore complex (NPC) requires Ran and is terminated at the nucleoplasmic side by its disassembly. The principal GTP exchange factor for Ran is the nuclear protein RCC1, whereas the major RanGAP is cytoplasmic, predicting that nuclear Ran is mainly in the GTP form and cytoplasmic Ran is in the GDP-bound form. Here, we show that nuclear import depends on cytoplasmic RanGDP and free GTP, and that RanGDP binds to the NPC. Therefore, import might involve nucleotide exchange and GTP hydrolysis on NPC-bound Ran. RanGDP binding to the NPC is not mediated by the Ran binding sites of importin-beta, suggesting that translocation is not driven from these sites. Consistently, a mutant importin-beta deficient in Ran binding can deliver its cargo up to the nucleoplasmic side of the NPC. However, the mutant is unable to release the import substrate into the nucleoplasm. Thus, binding of nucleoplasmic RanGTP to importin-beta probably triggers termination, i.e. the dissociation of importin-alpha from importin-beta and the subsequent release of the import substrate into the nucleoplasm. 相似文献
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Larry A. Jones Diane K. Jordan Kutay Taysi Arnold W. Strauss Joseph K. Toth 《Human genetics》1979,51(1):37-42
Summary A partial duplication of the distal segment of the long arm of chromosome 5 (q31qter) was observed in an infant with congenital malformations and dysmorphic features. The phenotypically normal father had a balanced translocation between the long arm of chromosome 5 and the short arm of chromosome 9: 46,XY,t(5;9)(q31;p24).The clinical and cytogenetic data obtained from six patients with partial duplications of two different long arm segments of chromosome 5 suggest that partial duplication of the distal long arm of chromosome 5 is associated with microcephaly, hypertelorism, epicanthus, strabismus, large upper lip, low-set, dysplastic ears, in addition to growth and psychomotor retardation. Partial duplication of the proximal part of the long arm of chromosome 5, on the other hand, is associated mainly with musculoskeletal abnormalities including muscle hypotrophy and hypotonia, scoliosis, lordosis, pectus carinatum, cubitus valgus, and genu valgum, in addition to psychomotor retardation. The dysmorphic features in this latter group include a bulging forehead, short nose, thick upper lip, low-set protruding ears and tapering, thin fingers. 相似文献
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Valentina Sanghez Maria Teresa Russo Maria Antonietta Ajmone‐Cat Emanuele Cacci Alberto Martire Patrizia Popoli Germana Falcone Flavia Michelini Marco Crescenzi Paolo Degan Luisa Minghetti Margherita Bignami Gemma Calamandrei 《Aging cell》2013,12(4):695-705
The contribution that oxidative damage to DNA and/or RNA makes to the aging process remains undefined. In this study, we used the hMTH1‐Tg mouse model to investigate how oxidative damage to nucleic acids affects aging. hMTH1‐Tg mice express high levels of the hMTH1 hydrolase that degrades 8‐oxodGTP and 8‐oxoGTP and excludes 8‐oxoguanine from both DNA and RNA. Compared to wild‐type animals, hMTH1‐overexpressing mice have significantly lower steady‐state levels of 8‐oxoguanine in both nuclear and mitochondrial DNA of several organs, including the brain. hMTH1 overexpression prevents the age‐dependent accumulation of DNA 8‐oxoguanine that occurs in wild‐type mice. These lower levels of oxidized guanines are associated with increased longevity and hMTH1‐Tg animals live significantly longer than their wild‐type littermates. Neither lipid oxidation nor overall antioxidant status is significantly affected by hMTH1 overexpression. At the cellular level, neurospheres derived from adult hMTH1‐Tg neural progenitor cells display increased proliferative capacity and primary fibroblasts from hMTH1‐Tg embryos do not undergo overt senescence in vitro. The significantly lower levels of oxidized DNA/RNA in transgenic animals are associated with behavioral changes. These mice show reduced anxiety and enhanced investigation of environmental and social cues. Longevity conferred by overexpression of a single nucleotide hydrolase in hMTH1‐Tg animals is an example of lifespan extension associated with healthy aging. It provides a link between aging and oxidative damage to nucleic acids. 相似文献
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E. Catão A. P. Castro C. C. Barreto R. H. Krüger C. M. Kyaw 《Archives of microbiology》2013,195(7):507-512
Although the richness of Bacteria and Fungi in Cerrado’ soils has been reported, here we report, for the first time, the archaeal community in Cerrado’s soils. DNA extracted from soil of two distinct vegetation types, a dense subtype of sensu strict (cerrado denso) and riverbank forest (mata de galeria), was used to amplify Archaea-specific 16S rRNA gene. All of the fragments sequenced were classified as Archaea into the phylum Thaumarchaeota, predominantly affiliated to groups I.1b and I.1c. Sequences affiliated to the group I.1a were found only in the soil from riverbank forest. Soils from ‘cerrado denso’ had greater Archaea richness than those from ‘mata de galeria’ based on the richness indexes and on the rarefaction curve. β-Diversity analysis showed significant differences between the sequences from the two soil areas studied because of their different thaumarchaeal group composition. These results provide information about the third domain of life from Cerrado soils. 相似文献
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Alexandra N. Myers Sara D. Lawhon Alison B. Diesel Charles W. Bradley Aline Rodrigues Hoffmann William J. Murphy Lives Cat Genome Consortium 《PLoS genetics》2022,18(2)
Dermatophytosis, also known as ringworm, is a contagious fungal skin disease affecting humans and animals worldwide. Persian cats exhibit severe forms of the disease more commonly than other breeds of cat, including other long-haired breeds. Certain types of severe dermatophytosis in humans are reportedly caused by monogenic inborn errors of immunity. The goal of this study was to identify genetic variants in Persian cats contributing to the phenotype of severe dermatophytosis. Whole-genome sequencing of case and control Persian cats followed by a genome-wide association study identified a highly divergent, disease-associated haplotype on chromosome F1 containing the S100 family of genes. S100 calcium binding protein A9 (S100A9), which encodes a subunit of the antimicrobial heterodimer known as calprotectin, contained 13 nonsynonymous variants between cases and controls. Evolutionary analysis of S100A9 haplotypes comparing cases, controls, and wild felids suggested the divergent disease-associated haplotype was likely introgressed into the domestic cat lineage and maintained via balancing selection. We demonstrated marked upregulation of calprotectin expression in the feline epidermis during dermatophytosis, suggesting involvement in disease pathogenesis. Given this divergent allele has been maintained in domestic cat and wildcat populations, this haplotype may have beneficial effects against other pathogens. The pathogen specificity of this altered protein should be investigated before attempting to reduce the allele frequency in the Persian cat breed. Further work is needed to clarify if severe Persian dermatophytosis is a monogenic disease or if hidden disease-susceptibility loci remain to be discovered. Consideration should be given to engineering antimicrobial peptides such as calprotectin for topical treatment of dermatophytosis in humans and animals. 相似文献
9.
Lipowsky G Bischoff FR Izaurralde E Kutay U Schäfer S Gross HJ Beier H Görlich D 《RNA (New York, N.Y.)》1999,5(4):539-549
10.
Jäggi RD Franco-Obregón A Mühlhäusser P Thomas F Kutay U Ensslin K 《Biophysical journal》2003,84(1):665-670
The nuclear pore complex (NPC) represents the only pathway for macromolecular communication between the nuclear and cytoplasmic compartments of the cell. Nucleocytoplasmic transport requires the interaction of transport receptors with phenylalanine-glycine (FG)-repeats that line the transport pathway through the NPC. Here we examine the effects of transport receptors and amphipathic alcohols on NPC topology using scanning force microscopy. We show that transport receptors that irreversibly bind FG-repeats increase NPC vertical aspect, whereas transport receptors that weakly interact with FG-repeats increase NPC diameter. Interestingly, small polar alcohols likewise increase NPC diameter. These opposing effects agree with the inhibition or enhancement of nuclear transport, respectively, previously ascribed to these agents. 相似文献