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81.
Gap junctions play critical roles in tissue function and homeostasis. Connexin43 (Cx43) is a major gap junction protein expressed in the mammalian heart and other tissues and may be regulated by its interaction with other cellular proteins. Using the yeast two-hybrid screen, we identified a novel Cx43-interacting protein of 85-kDa, CIP85, which contains a single TBC, SH3, and RUN domain, in addition to a short coiled coil region. Homologues containing this unique combination of domains were found in human, D. melanogaster, and C. elegans. CIP85 mRNA is expressed ubiquitously in mouse and human tissues. In vitro interaction assays and in vivo co-immunoprecipitation experiments confirmed the interaction of endogenous CIP85 with Cx43. In vitro interaction experiments using CIP85 mutants with in-frame deletions of the TBC, SH3, and RUN domains indicated that the SH3 domain of CIP85 is involved in its interaction with Cx43. Conversely, analysis of Cx43 mutants with proline to alanine substitutions in the two proline-rich regions of Cx43 revealed that the P(253)LSP(256) motif is an important determinant of the ability of Cx43 to interact with CIP85. Laser-scanning confocal microscopy showed that CIP85 colocalized with Cx43 at the cell periphery, particularly in areas reminiscent of gap junction plaques. The functional importance of the interaction between CIP85 and Cx43 was suggested by the observation that CIP85 appears to induce the turnover of Cx43 through the lysosomal pathway. 相似文献
82.
83.
Molecular basis of inward rectification: polyamine interaction sites located by combined channel and ligand mutagenesis 下载免费PDF全文
Kurata HT Phillips LR Rose T Loussouarn G Herlitze S Fritzenschaft H Enkvetchakul D Nichols CG Baukrowitz T 《The Journal of general physiology》2004,124(5):541-554
Polyamines cause inward rectification of (Kir) K+ channels, but the mechanism is controversial. We employed scanning mutagenesis of Kir6.2, and a structural series of blocking diamines, to combinatorially examine the role of both channel and blocker charges. We find that introduced glutamates at any pore-facing residue in the inner cavity, up to and including the entrance to the selectivity filter, can confer strong rectification. As these negative charges are moved higher (toward the selectivity filter), or lower (toward the cytoplasm), they preferentially enhance the potency of block by shorter, or longer, diamines, respectively. MTSEA+ modification of engineered cysteines in the inner cavity reduces rectification, but modification below the inner cavity slows spermine entry and exit, without changing steady-state rectification. The data provide a coherent explanation of classical strong rectification as the result of polyamine block in the inner cavity and selectivity filter. 相似文献
84.
Tsuji F Ishihara A Kurata K Nakagawa A Okada M Kitamura S Kanamaru K Masuda Y Murakami K Irie K Sakagami Y 《FEBS letters》2012,586(2):174-179
ComX pheromone is an isoprenoidal oligopeptide containing a modified tryptophan residue, which stimulates natural genetic competence in the gram-positive bacterium Bacillus. Since posttranslational prenylation on the tryptophan residue has not been reported except in ComX pheromone, the universality of this modification has not yet been elucidated. In this paper, we established a cell-free system, whereby the tryptophan residue in peptides is modified with a geranyl group by modifying enzyme ComQ. In addition, we investigated enzymatic reaction conditions using an in vitro enzyme reaction system. This is the first report of in vitro geranylation on the tryptophan residue. This system is potentially a useful tool for elucidating the universality of prenylation on the tryptophan residue. 相似文献
85.
Mao Nagasawa Yumi Ogino Koji Kurata Tsuyoshi Otsuka Jyunki Yoshida Shozo Tomonaga Mitsuhiro Furuse 《Amino acids》2012,43(5):2101-2111
While abnormalities in monoamine metabolism have been investigated heavily per potential roles in the mechanisms of depression, the contribution of amino acid metabolism in the brain remains not well understood. In additional, roles of the hypothalamus–pituitary–adrenal axis in stress-regulation mechanisms have been of much focus, while the contribution of central amino acid metabolism to these mechanisms has not been well appreciated. Therefore, whether depression-like states affect amino acid metabolism and their potential roles on stress-regulatory mechanisms were investigated by comparing Wistar Kyoto rats, which display depression-like behaviors and stress vulnerability, to control Wistar rats. Brain amino acid metabolism in Wistar Kyoto rats was greatly different from normal Wistar rats, with special reference to lower cystathionine and serine levels. In addition, Wistar Kyoto rats demonstrated abnormality in dopamine metabolism compared with Wistar rats. In the case of stress response, amino acid levels having a sedative and/or hypnotic effect were constant in the brain of Wistar Kyoto rats, though these amino acid levels were reduced in Wistar rats under a stressful condition. These results suggest that the abnormal amino acid metabolism may induce depression-like behaviors and stress vulnerability in Wistar Kyoto rats. Therefore, we hypothesized that abnormalities in amino acid and monoamine metabolism may induce depression, and amino acid metabolism in the brain may be related to stress vulnerability. 相似文献
86.
Malon C Brachtel E Cosatto E Graf HP Kurata A Kuroda M Meyer JS Saito A Wu S Yagi Y 《Analytical cellular pathology (Amsterdam)》2012,35(2):97-100
Despite the prognostic importance of mitotic count as one of the components of the Bloom-Richardson grade, several studies have found that pathologists' agreement on the mitotic grade is fairly modest. Collecting a set of more than 4,200 candidate mitotic figures, we evaluate pathologists' agreement on individual figures, and train a computerized system for mitosis detection, comparing its performance to the classifications of three pathologists. The system's and the pathologists' classifications are based on evaluation of digital micrographs of hematoxylin and eosin stained breast tissue. On figures where the majority of pathologists agree on a classification, we compare the performance of the trained system to that of the individual pathologists. We find that the level of agreement of the pathologists ranges from slight to moderate, with strong biases, and that the system performs competitively in rating the ground truth set. This study is a step towards automatic mitosis count to accelerate a pathologist's work and improve reproducibility. 相似文献
87.
Masaru?TanakaEmail author Yasuhiro?Takahata Rie?Kurata Hiroki?Nakayama Masaru?Yoshinaga 《Molecular breeding : new strategies in plant improvement》2012,29(3):565-574
To elucidate further the genetic mechanism underlying anthocyanin accumulation in the storage roots of recent Japanese purple-fleshed
sweetpotato cultivars, we compared the structure of the IbMYB1 gene in cultivar Ayamurasaki and its spontaneous mutant, AYM96, whose storage roots do not accumulate anthocyanin. Amplification
of the IbMYB1 genomic fragment covering the coding sequences suggested that the genome of Ayamurasaki contained three types of IbMYB1 sequences, named IbMYB1-1, IbMYB1-2a and IbMYB1-2b, whereas AYM96 had only IbMYB1-1. Although these three IbMYB1 sequences had identical coding sequences, IbMYB1-1 had a 7-bp insertion in the first intron. IbMYB1-2a and IbMYB1-2b were characterized by a single nucleotide polymorphism in the second intron. Further cloning and sequencing of the flanking
regions of these IbMYB1 sequences showed that the promoter and 3′ flanking regions of IbMYB1-2a and IbMYB1-2b were different from those of IbMYB1-1. Genetic analysis using an F1 population derived from a cross between the purple-fleshed cultivar Murasakimasari and AYM96 suggested that IbMYB1-2 sequences are responsible for anthocyanin accumulation in the storage roots. The structural features of these three IbMYB1 sequences and identification of the IbMYB1-2null sequence, which contained sequences very similar to those of the flanking regions of IbMYB1-2a and IbMYB1-2b, but which lacked the sequence around the coding region, suggested that IbMYB1 genes in recent Japanese purple-fleshed cultivars had been established through multiple gene-duplication events. 相似文献
88.
K Inoue K Maeda Y Kato S Tonami S Takagi H Kurata 《Source code for biology and medicine》2012,7(1):9-4
ABSTRACT: Computer simulation has been an important technique to capture the dynamics of biochemical networks. In most networks, however, few kinetic parameters have been measured in vivo because of experimental complexity. We develop a kinetic parameter estimation system, named the CADLIVE Optimizer, which comprises genetic algorithms-based solvers with a graphical user interface. This optimizer is integrated into the CADLIVE Dynamic Simulator to attain efficient simulation for dynamic models. 相似文献
89.
Reevaluation and Reduction of a PCR Bias Caused by Reannealing of Templates 总被引:4,自引:1,他引:3 下载免费PDF全文
Shinya Kurata Takahiro Kanagawa Yukio Magariyama Kyoko Takatsu Kazutaka Yamada Toyokazu Yokomaku Yoichi Kamagata 《Applied microbiology》2004,70(12):7545-7549
We reevaluated the bias toward a 1:1 ratio of products in multitemplate PCR used in ecological studies and showed that the template reannealing at the annealing step would not cause the bias; however, the preferential homoduplex formation during temperature decrease from denaturation to annealing step would cause the bias. 相似文献
90.
Among the many species that grow in New Caledonia, the pitcher plant Nepenthes vieillardii (Nepenthaceae) has a high degree of morphological variation. In this study, we present the patterns of genetic differentiation of pitcher plant populations based on chloroplast DNA haplotype analysis using the sequences of five spacers. We analyzed 294 samples from 16 populations covering the entire range of the species, using 4660 bp of sequence. Our analysis identified 17 haplotypes, including one that is widely distributed across the islands, as well as regional and private haplotypes. The greatest haplotype diversity was detected on the eastern coast of the largest island and included several private haplotypes, while haplotype diversity was low in the southern plains region. The parsimony network analysis of the 17 haplotypes suggested that the genetic divergence is the result of long-term isolation of individual populations. Results from a spatial analysis of molecular variance and a cluster analysis suggest that the plants once covered the entire serpentine area of New Caledonia and that subsequent regional fragmentation resulted in the isolation of each population and significantly restricted seed flow. This isolation may have been an important factor in the development of the morphological and genetic variation among pitcher plants in New Caledonia. 相似文献