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1.
Kole T. Roybal Emily M. Mace Danielle J. Clark Alan D. Leard Andrew Herman Paul Verkade Jordan S. Orange Christoph Wülfing 《PloS one》2015,10(8)
Dynamic subcellular distributions of signaling system components are critical regulators of cellular signal transduction through their control of molecular interactions. Understanding how signaling activity depends on such distributions and the cellular structures driving them is required for comprehensive insight into signal transduction. In the activation of primary murine T cells by antigen presenting cells (APC) signaling intermediates associate with various subcellular structures, prominently a transient, wide, and actin-associated lamellum extending from an interdigitated T cell:APC interface several micrometers into the T cell. While actin dynamics are well established as general regulators of cellular organization, their role in controlling signaling organization in primary T cell:APC couples and the specific cellular structures driving it is unresolved. Using modest interference with actin dynamics with a low concentration of Jasplakinolide as corroborated by costimulation blockade we show that T cell actin preferentially controls lamellal signaling localization and activity leading downstream to calcium signaling. Lamellal localization repeatedly related to efficient T cell function. This suggests that the transient lamellal actin matrix regulates T cell signaling associations that facilitate T cell activation. 相似文献
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Mohammed Mamdani Vernell Williamson Gowon O. McMichael Tana Blevins Fazil Aliev Amy Adkins Laura Hack Tim Bigdeli Andrew D. van der Vaart Bradley Todd Web Silviu-Alin Bacanu Gursharan Kalsi COGA Consortium Kenneth S. Kendler Michael F. Miles Danielle Dick Brien P. Riley Catherine Dumur Vladimir I. Vladimirov 《PloS one》2015,10(9)
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Zhijiang Yan Mathieu Delannoy Chen Ling Danielle Daee Fekret Osman Parameswary A. Muniandy Xi Shen Anneke B. Oostra Hansen Du Jurgen Steltenpool Ti Lin Beatrice Schuster Chantal Décaillet Andrzej Stasiak Alicja Z. Stasiak Stacie Stone Maureen E. Hoatlin Detlev Schindler Christopher L. Woodcock Hans Joenje Weidong Wang 《Molecular cell》2010,37(6):865-878
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Disaccharide uptake by brush-border membrane vesicles lacking the corresponding hydrolases 总被引:3,自引:0,他引:3
Intestinal disaccharide uptake was studied with isolated brush-border membrane vesicles lacking the corresponding hydrolase. Either 15-day-old chick intestine, lacking both trehalase and lactase, or newborn pig intestine, lacking sucrase, was used. Both animal species yielded osmotically active vesicles capable of D-glucose/Na+ cotransport with a positive overshoot test. Vesicles from either origin gave quantitatively similar results in regard to both initial uptake rates and relative vesicle volumes. The nontransported analogs D-mannitol and L-glucose were used as diffusion markers. When tested with the appropriate disaccharidase-lacking vesicles, lactose, trehalose and sucrose exhibited uptake rates indistinguishable from those of D-mannitol and L-glucose. These uptakes were unaffected by the presence or absence of Na+, phlorizin and Tris. Chromatographic analysis confirmed the lack of hydrolysis of each disaccharide after prolonged incubation. The inescapable conclusion seems to be that intact disaccharides are not transported through the brush-border membrane, their uptake occurring through simple diffusion. 相似文献
9.
Conformation of the glucotriose unit in the lipid-linked oligosaccharide precursor for protein glycosylation. 总被引:1,自引:0,他引:1
The conformation of the glucotriose unit of the protein glycosylation precursor Glc3Man9GlcNAc2 was assessed by deuterium exchange studies on the model tetrasaccharide alpha Glc----2 alpha Glc----3 alpha Glc----3 alpha Man----OCH2CH2CH3 dissolved in deuterated dimethyl sulfoxide. The hydroxyl proton on C-2 of the nonreducing end glucose and on C-4 of the glucose attached to mannose both show dramatic isotope shifts indicative of a strong hydrogen bond between these two hydroxyl groups. Such a hydrogen bond requires a fixed conformation of the glucotriose unit that brings these hydroxyl groups within 3 A of each other, a conformation that is supported by molecular modeling based on hard-sphere exo-anomeric (HSEA) calculations. The temperature dependence of the hydroxyl proton chemical shifts supports the postulated hydrogen bond, and the torsional angles between the three glucose units derived from the HSEA calculations are consistent with results from related studies on other saccharides. The results support a model for biochemical function in which the glucotriose unit could modulate the activity of the oligosaccharyltransferase by binding in a fixed conformation to a specific effector site in the enzyme. 相似文献
10.
L Ballou E Alvarado P K Tsai A Dell C E Ballou 《The Journal of biological chemistry》1989,264(20):11857-11864
Total cell mannoprotein was isolated from Saccharomyces cerevisiae X2180 mutants that have defects in elongation of the outer chain attached to the N-linked core oligosaccharides (mnn7, mnn8, mnn9, and mnn10) (Ballou, L., Cohen, R. E., and Ballou, C. E. (1980) J. Biol. Chem. 255, 5986-5991). Comparison of the oligosaccharides released by endoglucosaminidase H digestion confirmed that the mnn9 mutation eliminates all but two mannoses of the outer chain, whereas the mnn8 and mnn10 strains produce outer chains of variable but similar lengths. The isolate designated mnn7 was found to be allelic with mnn8. Haploid mutants of the type mnn8 mnn9 or mnn9 mnn10 had the mnn9 phenotype, which established that the mnn9 defect is dominant and presumably acts at a processing step prior to the steps affected by mnn8 and mnn10. Analysis of the mnn1 mnn2 mnn10 oligosaccharides revealed that the heterogeneous outer chain contained 6-16 alpha 1----6-linked mannose units and each was terminated by a single alpha 1----2-linked mannose unit, whereas the core lacked one such unit that was present in the mnn9 oligosaccharide. The results are consistent with and support the hypothesis (Gopal, P. K., and Ballou, C. E. (1988) Proc. Natl. Acad. Sci. U.S.A. 84, 8824-8828) that addition of such a side-chain mannose unit is associated with termination of outer chain elongation in these mutants and may serve as a stop signal that regulates outer chain synthesis in the parent wild-type strain. 相似文献