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61.
Jonathan P. Belman Rachel R. Bian Estifanos N. Habtemichael Don T. Li Michael J. Jurczak Abel Alcázar-Román Leah J. McNally Gerald I. Shulman Jonathan S. Bogan 《The Journal of biological chemistry》2015,290(7):4447-4463
Insulin causes the exocytic translocation of GLUT4 glucose transporters to stimulate glucose uptake in fat and muscle. Previous results support a model in which TUG traps GLUT4 in intracellular, insulin-responsive vesicles termed GLUT4 storage vesicles (GSVs). Insulin triggers TUG cleavage to release the GSVs; GLUT4 then recycles through endosomes during ongoing insulin exposure. The TUG C terminus binds a GSV anchoring site comprising Golgin-160 and possibly other proteins. Here, we report that the TUG C terminus is acetylated. The TUG C-terminal peptide bound the Golgin-160-associated protein, ACBD3 (acyl-CoA-binding domain-containing 3), and acetylation reduced binding of TUG to ACBD3 but not to Golgin-160. Mutation of the acetylated residues impaired insulin-responsive GLUT4 trafficking in 3T3-L1 adipocytes. ACBD3 overexpression enhanced the translocation of GSV cargos, GLUT4 and insulin-regulated aminopeptidase (IRAP), and ACBD3 was required for intracellular retention of these cargos in unstimulated cells. Sirtuin 2 (SIRT2), a NAD+-dependent deacetylase, bound TUG and deacetylated the TUG peptide. SIRT2 overexpression reduced TUG acetylation and redistributed GLUT4 and IRAP to the plasma membrane in 3T3-L1 adipocytes. Mutation of the acetylated residues in TUG abrogated these effects. In mice, SIRT2 deletion increased TUG acetylation and proteolytic processing. During glucose tolerance tests, glucose disposal was enhanced in SIRT2 knock-out mice, compared with wild type controls, without any effect on insulin concentrations. Together, these data support a model in which TUG acetylation modulates its interaction with Golgi matrix proteins and is regulated by SIRT2. Moreover, acetylation of TUG enhances its function to trap GSVs within unstimulated cells and enhances insulin-stimulated glucose uptake. 相似文献
62.
Brd2/RING3 interacts with a chromatin-binding domain in the Kaposi's Sarcoma-associated herpesvirus latency-associated nuclear antigen 1 (LANA-1) that is required for multiple functions of LANA-1 下载免费PDF全文
Viejo-Borbolla A Ottinger M Brüning E Bürger A König R Kati E Sheldon JA Schulz TF 《Journal of virology》2005,79(21):13618-13629
63.
The arylhydrocarbon receptor (AhR) pathway is known to be critical for cellular events, especially for those evoked by several environmental chemicals such as 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD). Whereas the function of the AhR in TCDD toxicity is well analyzed, the importance of the recently cloned AhRR in the TCDD-stimulated AhR signaling cascade is still unclear. In mammalian tissues, the AhRR gene seems to be ubiquitously expressed and its expression is altered by various AhR ligands. Basal and induced AhRR mRNA levels were found to be highly cell-, tissue- and species-specific. An inhibitory activity of the AhRR on AhR signaling was proposed from overexpression studies. However, there are not sufficient data showing such functional activity of the AhRR in vivo. This short overview summarizes the present knowledge about the AhRR and should stimulate research in the AhRR field to elucidate its physiological function and its toxicological importance in dioxin toxicity. 相似文献
64.
The crystal structure of the seed lectin from the tropical legume Bowringia milbraedii was determined in complex with the disaccharide ligand Man(alpha1-2)Man. In solution, the protein exhibits a dynamic dimer-tetramer equilibrium, consistent with the concanavalin A-type tetramer observed in the crystal. Contacts between the tetramers are mediated almost exclusively through the carbohydrate ligand, resulting in a crystal lattice virtually identical to that of the concanavalin-A:Man(alpha1-2)Man complex, even though both proteins have less than 50% sequence identity. The disaccharide binds exclusively in a "downstream" binding mode, with the non-reducing mannose occupying the monosaccharide-binding site. The reducing mannose is bound in a predominantly polar subsite involving Tyr131, Gln218, and Tyr219. 相似文献
65.
A model optical immunosensor was developed to quantify an antibody present in a sample by measuring the fluorescence of Cyanine-5 conjugated with the antibody, using a competitive and a sandwich immunoreaction configuration, with the antigen immobilised in controlled pore glass beads. At pH 2, 94% of the antigen-antibody complex was dissociated, allowing reutilisation. Photobleaching had no effect on the fluorescence. This model system was used to detect Brucella sp. infection and could quantify anti-Brucella sp. antibodies in ovine serum samples in the range from 0.005 to 0.11 mg ml(-1). 相似文献
66.
Johnna M. Frierson Andrea J. Pruijssers Jennifer L. Konopka Dirk M. Reiter Ty W. Abel Thilo Stehle Terence S. Dermody 《Journal of virology》2012,86(24):13164-13173
Mammalian reoviruses display serotype-specific patterns of tropism and disease in the murine central nervous system (CNS) attributable to polymorphisms in viral attachment protein σ1. While all reovirus serotypes use junctional adhesion molecule-A as a cellular receptor, they differ in their utilization of carbohydrate coreceptors. This observation raises the possibility that carbohydrate binding by σ1 influences reovirus pathology in the CNS. In this study, we sought to define the function of carbohydrate binding in reovirus neuropathogenesis. Newborn mice were inoculated intramuscularly with wild-type strain type 3 Dearing (T3D) and T3D-σ1R202W, a point mutant T3D derivative that does not bind sialic acid (SA). Infected mice were monitored for survival, and viral loads at the sites of primary and secondary replication were quantified. Fewer mice inoculated with the wild-type virus survived in comparison to those inoculated with the mutant virus. The wild-type virus also produced higher titers in the spinal cord and brain at late times postinoculation but lower titers in the liver in comparison to those produced by the mutant virus. In addition, the wild-type virus was more virulent and produced higher titers in the brain than the mutant following intracranial inoculation. These animal infectivity studies suggest that T3D-σ1R202W harbors a defect in neural growth. Concordantly, compared with the wild-type virus, the mutant virus displayed a decreased capacity to infect and replicate in primary cultures of cortical neurons, a property dependent on cell surface SA. These results suggest that SA binding enhances the kinetics of reovirus replication in neural tissues and highlight a functional role for sialylated glycans as reovirus coreceptors in the CNS. 相似文献
67.
Véronique David Panos Papadopoulos Jacqueline Yaouanq Martine Blayau Laurent Abel Elizabetta Zappone Muriel Perichon Jim Drysdale Jean-Yves Le Gall Marcel Simon 《Human genetics》1989,82(2):123-126
Summary We have analysed karyotypes and DNA from three patients with aniridia (congenital absence of irises) and Wilms' tumour. All three had constitutional deletions from the short arm of chromosome 11. The minimum region of overlap of the deletion involves a small region of band 11p13 presumed to contain the genetic loci responsible for both phenotypic abnormalities. Using cells from these patients, somatic cell hybrids with transformed mouse cells have been prepared. Individual subclones retaining either the deletion-11 chromosome or the normal chromosome 11, in addition to a variety of other human chromosomes, have been identified. The relative position of these breakpoints have been determined and the panel of hybrids has been used to map randomly-isolated 11p13 DNA sequences. The characterisation of these deletions has provided a useful panel of hybrids for random mapping strategies designed to identify the Wilms' and aniridia genes. 相似文献
68.
Masashi Yamaguchi Theodore Yanos Tomoko Yamaguchi Abel Lajtha 《Developmental neurobiology》1969,1(4):419-433
When rat sciatic nerves were incubated with C14l-lysine, l- or d-glutamate, or d-l γ-aminoisobutyrate, the labeled compounds penetrated the nerve, and the level of lysine and leucine after 1 hr was higher in the nerve than in the medium. The level increased with time, and at 24 hr glutamate levels also were higher in the nerve than in the medium. Lowering the temperature strongly inhibited uptake, while other conditions such as absence of glucose, absence of sodium, or the presence of cyanide inhibited uptake by nerve less than uptake by brain slices. The uptake against a concentration gradient, and inhibitions of this uptake by metabolic inhibitors and by structural analogs, were interpreted as showing the presence of transport processes for amino acids in peripheral nerves with characteristics similar to such transport processes in the central nervous system. 相似文献
69.
Alireza Badiei Jack Rivers-Auty Abel Damien Ang Madhav Bhatia 《Applied microbiology and biotechnology》2013,97(17):7845-7852
Hydrogen sulfide is an inflammatory mediator and is produced by the activity of the enzyme cystathionine γ-lyase (CSE) in macrophages. Previously, pharmacological inhibition of CSE has been reported to have conflicting results, and this may be due to the lack of specificity of the pharmacological agents. Therefore, this study used a very specific approach of small interfering RNA (siRNA) to inhibit the production of the CSE in an in vitro setting. We found that the activation of macrophages by lipopolysaccharide (LPS) resulted in higher levels of CSE mRNA and protein as well as the increased production of proinflammatory cytokines and nitric oxide (NO). We successfully used siRNA to specifically reduce the levels of CSE mRNA and protein in activated macrophages. Furthermore, the levels of proinflammatory cytokines in LPS-activated macrophages were significantly lower in siRNA-transfected cells compared to those in untransfected controls. However, the production levels of NO by the transfected cells were higher, suggesting that CSE activity has an inhibitory effect on NO production. These findings suggest that the CSE enzyme has a crucial role in the activation of macrophages, and its activity has an inhibitory effect on NO production by these cells. 相似文献
70.