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51.
SCRAPPER-dependent ubiquitination of active zone protein RIM1 regulates synaptic vesicle release 总被引:1,自引:0,他引:1
Yao I Takagi H Ageta H Kahyo T Sato S Hatanaka K Fukuda Y Chiba T Morone N Yuasa S Inokuchi K Ohtsuka T Macgregor GR Tanaka K Setou M 《Cell》2007,130(5):943-957
Little is known about how synaptic activity is modulated in the central nervous system. We have identified SCRAPPER, a synapse-localized E3 ubiquitin ligase, which regulates neural transmission. SCRAPPER directly binds and ubiquitinates RIM1, a modulator of presynaptic plasticity. In neurons from Scrapper-knockout (SCR-KO) mice, RIM1 had a longer half-life with significant reduction in ubiquitination, indicating that SCRAPPER is the predominant ubiquitin ligase that mediates RIM1 degradation. As anticipated in a RIM1 degradation defect mutant, SCR-KO mice displayed altered electrophysiological synaptic activity, i.e., increased frequency of miniature excitatory postsynaptic currents. This phenotype of SCR-KO mice was phenocopied by RIM1 overexpression and could be rescued by re-expression of SCRAPPER or knockdown of RIM1. The acute effects of proteasome inhibitors, such as upregulation of RIM1 and the release probability, were blocked by the impairment of SCRAPPER. Thus, SCRAPPER has an essential function in regulating proteasome-mediated degradation of RIM1 required for synaptic tuning. 相似文献
52.
Targeted deletion of AIF decreases mitochondrial oxidative phosphorylation and protects from obesity and diabetes 总被引:8,自引:0,他引:8
Pospisilik JA Knauf C Joza N Benit P Orthofer M Cani PD Ebersberger I Nakashima T Sarao R Neely G Esterbauer H Kozlov A Kahn CR Kroemer G Rustin P Burcelin R Penninger JM 《Cell》2007,131(3):476-491
Type-2 diabetes results from the development of insulin resistance and a concomitant impairment of insulin secretion. Recent studies place altered mitochondrial oxidative phosphorylation (OxPhos) as an underlying genetic element of insulin resistance. However, the causative or compensatory nature of these OxPhos changes has yet to be proven. Here, we show that muscle- and liver-specific AIF ablation in mice initiates a pattern of OxPhos deficiency closely mimicking that of human insulin resistance, and contrary to current expectations, results in increased glucose tolerance, reduced fat mass, and increased insulin sensitivity. These results are maintained upon high-fat feeding and in both genetic mosaic and ubiquitous OxPhos-deficient mutants. Importantly, the effects of AIF on glucose metabolism are acutely inducible and reversible. These findings establish that tissue-specific as well as global OxPhos defects in mice can counteract the development of insulin resistance, diabetes, and obesity. 相似文献
53.
Protein kinase C delta regulates the phosphorylation of heat shock protein 27 in human hepatocellular carcinoma 总被引:1,自引:0,他引:1
Takai S Matsushima-Nishiwaki R Tokuda H Yasuda E Toyoda H Kaneoka Y Yamaguchi A Kumada T Kozawa O 《Life sciences》2007,81(7):585-591
We have recently reported that attenuated phosphorylation of heat shock protein (HSP) 27 correlates with tumor progression in patients with hepatocellular carcinoma (HCC). In the present study, we investigated what kind of kinase regulates phosphorylation of HSP27 in human HCC-derived HuH7 cells. 12-O-tetradecanoylphorbol-13-acetate (TPA) and 1-oleoyl-2-acetylglycerol, direct activators of protein kinase C (PKC), markedly strengthened the phosphorylation of HSP27. Bisindorylmaleimide I, an inhibitor of PKC, suppressed the TPA-induced levels of HSP27 phosphorylation in addition to its basal levels. Knock down of PKCdelta suppressed HSP27 phosphorylation, as well as p38 mitogen-activated protein kinase (MAPK) phosphorylation. SB203580, an inhibitor of p38 MAPK, suppressed the TPA-induced HSP27 phosphorylation. Our results strongly suggest that activation of PKCdelta regulates the phosphorylation of HSP27 via p38 MAPK in human HCC. 相似文献
54.
Huang M Ida H Arima K Nakamura H Aramaki T Fujikawa K Tamai M Kamachi M Kawakami A Yamasaki H Origuchi T Eguchi K 《Life sciences》2007,81(19-20):1461-1466
Our recent report demonstrated that apoptosis-specific autoantibodies against granzyme B-induced cleavage fragments of SS-B (La) were found in the sera from patients with primary Sj?gren's syndrome. The objective of this study was identified by the intracellular redistribution of La autoantigen during granzyme B-induced apoptosis. We developed green fluorescence protein (GFP)-La and GFP-LaDelta220 (generation of granzyme B-specific cleavage of La protein) fusion proteins. GFP-La protein was localized in the nucleus, whereas the GFP-LaDelta220 protein predominantly existed in the cytoplasm in transformed A293T cells. Nuclear GFP-La protein was translocated to cytoplasm after granzyme B enriched YT cells incubation. La protein in human salivary grand HSG cells is cleaved and translocated from the nucleus to the cytoplasm after YT cell co-cultivation. These results suggest that La protein is cleaved by granzyme B and N-terminal La fragment (27 kD) translocated to the cytoplasm, thus leading to a novel autoantibody production during granzyme B-mediated cytotoxicity. 相似文献
55.
Social conditions and function of inter-group movement of females of the polygynous goby, Trimma okinawae, have been studied at Akamizu Beach, Kagoshima, Japan. Some females moved from their original groups, where the male was
still present, to other groups. Before the movement females sometimes temporarily visited the group into which they subsequently
moved, suggesting they were able to assess social conditions during the visit. By moving, the females increased in size rank
or escaped from similar-sized female competitors in their previous groups. Although the social ranks of the moving females
in their original groups were lower than those of the resident females, the ratio of the number of females that changed sex
to the number of females surviving at the end of the study did not differ for the two types of female. Inter-group movement
of females may increase the probability of their changing sex to become a dominant male. 相似文献
56.
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58.
Wild‐type and specific mutant androgen receptor mediates transcription via 17β‐estradiol in sex hormone‐sensitive cancer cells
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Takao Susa Reina Ikaga Takashi Kajitani Masayoshi Iizuka Hiroko Okinaga Mimi Tamamori‐Adachi Tomoki Okazaki 《Journal of cellular physiology》2015,230(7):1594-1606
We previously encountered regulatory processes wherein dihydrotestosterone (DHT) exerted its inhibitory effect on parathyroid hormone‐related protein (PTHrP) gene repression through the estrogen receptor (ER)α, but not the androgen receptor (AR), in breast cancer MCF‐7 cells. Here, we investigated whether such aberrant ligand‐nuclear receptor (NR) interaction is present in prostate cancer LNCaP cells. First, we confirmed that LNCaP cells expressed large amounts of AR at negligible levels of ERα/β or progesterone receptor. Both suppression of PTHrP and activation of prostate‐specific antigen genes were observed after independent administration of 17β‐estradiol (E2), DHT, or R5020. Consistent with the notion that the LNCaP AR lost its ligand specificity due to a mutation (Thr‐Ala877), experiments with siRNA targeting the respective NR revealed that the AR monopolized the role of the mediator of shared hormone‐dependent regulation, which was invariably associated with nuclear translocation of this mutant AR. Microarray analysis of gene regulation by DHT, E2, or R5020 disclosed that more than half of the genes downstream of the AR (Thr‐Ala877) overlapped in the LNCaP cells. Of particular interest, we realized that the AR (wild‐type [wt]) and AR (Thr‐Ala877) were equally responsible for the E2‐AR interactions. Fluorescence microscopy experiments demonstrated that both EGFP‐AR (wt) and EGFP‐AR (Thr‐Ala877) were exclusively localized within the nucleus after E2 or DHT treatment. Furthermore, reporter assays revealed that some other cancer cells exhibited aberrant E2‐AR (wt) signaling similar to that in the LNCaP cells. We herein postulate the presence of entangled interactions between wt AR and E2 in certain hormone‐sensitive cancer cells. J. Cell. Physiol. 230: 1594–1606, 2015. © 2014 The Authors. Journal of Cellular Physiology Published by Wiley Periodicals, Inc. 相似文献
59.
In this study, we analyzed structural features of the N-glycans linked to glycoproteins expressed in various edible beans to identify excellent sources of useful N-glycans and N-glycopeptides. Structural analysis of N-glycans of the glycopeptides prepared from the pepsin digests of bean powder that the useful high-mannose type N-glycans occur predominantly in Phaseolus and Vigna beans; tora bean for Man?GlcNAc?-Asn, dainagon bean for Man?GlcNAc?-Asn, and azuki bean for Man?GlcNAc?-Asn. 相似文献
60.
Mitsui H Aoyama T Furu M Ito K Jin Y Maruyama T Kanaji T Fujimura S Sugihara H Nishiura A Otsuka T Nakamura T Toguchida J 《Arthritis research & therapy》2011,13(5):R146-13