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991.
Michael R. Heaven Anthony W. Herren Daniel L. Flint Natasha L. Pacheco Jiangtao Li Alice Tang Fatima Khan James E. Goldman Brett S. Phinney Michelle L. Olsen 《Molecular & cellular proteomics : MCP》2022,21(1):100180
Alexander disease (AxD) is a rare and fatal neurodegenerative disorder caused by mutations in the gene encoding glial fibrillary acidic protein (GFAP). In this report, a mouse model of AxD (GFAPTg;Gfap+/R236H) was analyzed that contains a heterozygous R236H point mutation in murine Gfap as well as a transgene with a GFAP promoter to overexpress human GFAP. Using label-free quantitative proteomic comparisons of brain tissue from GFAPTg;Gfap+/R236H versus wild-type mice confirmed upregulation of the glutathione metabolism pathway and indicated proteins were elevated in the peroxisome proliferator-activated receptor (PPAR) signaling pathway, which had not been reported previously in AxD. Relative protein-level differences were confirmed by a targeted proteomics assay, including proteins related to astrocytes and oligodendrocytes. Of particular interest was the decreased level of the oligodendrocyte protein, 2-hydroxyacylsphingosine 1-beta-galactosyltransferase (Ugt8), since Ugt8-deficient mice exhibit a phenotype similar to GFAPTg;Gfap+/R236H mice (e.g., tremors, ataxia, hind-limb paralysis). In addition, decreased levels of myelin-associated proteins were found in the GFAPTg;Gfap+/R236H mice, consistent with the role of Ugt8 in myelin synthesis. Fabp7 upregulation in GFAPTg;Gfap+/R236H mice was also selected for further investigation due to its uncharacterized association to AxD, critical function in astrocyte proliferation, and functional ability to inhibit the anti-inflammatory PPAR signaling pathway in models of amyotrophic lateral sclerosis (ALS). Within Gfap+ astrocytes, Fabp7 was markedly increased in the hippocampus, a brain region subjected to extensive pathology and chronic reactive gliosis in GFAPTg;Gfap+/R236H mice. Last, to determine whether the findings in GFAPTg;Gfap+/R236H mice are present in the human condition, AxD patient and control samples were analyzed by Western blot, which indicated that Type I AxD patients have a significant fourfold upregulation of FABP7. However, immunohistochemistry analysis showed that UGT8 accumulates in AxD patient subpial brain regions where abundant amounts of Rosenthal fibers are located, which was not observed in the GFAPTg;Gfap+/R236H mice. 相似文献
992.
Summary The ratio between the unidirectional fluxes of K+ across the frog skin with K-permeable outer membranes was determined in the absence of Na+ in the apical solutions. The experiments were performed under presteady-state conditions to be able to separate the flux ratio for K+ through the cells from contributions to the fluxes through extracellular leaks. The cellular flux ratio deviated strongly from the value calculated from the flux ratio for electrodiffusion. The experiments can be explained if the passive K transport through the epithelial cells proceeds through specific channels by single-file diffusion with a flux ratio exponent of about 2.5. 相似文献
993.
Oussama El Far Béatrice Marquèze Christian Leveque Nicole Martin-Moutôt Bethan Lang John Newsom-Davis †Akira Yoshida †Masami Takahashi Michael J. Seagar 《Journal of neurochemistry》1995,64(4):1696-1702
Abstract: In Lambert-Eaton myasthenic syndrome neurotransmitter release is reduced by an autoimmune response directed against the calcium channel complex of the nerve terminal. Autoantibodies were detected by immunoprecipitation assays using solubilized receptors labeled with ligands selective for N-type (125 I-ω conotoxin GVIA) and L-type ([3 H]PN200-110) calcium channels. Sera with a high antibody titer (>3 n M ) against rat brain N-type channels contained autoantibodies that immunoprecipitated neuronal and muscle L-type channels. These IgG fractions stained a 55-kDa protein in immunoblots of purified skeletal muscle dihydropyridine receptor, suggesting that they contain autoantibodies against the β subunit of the calcium channel. A distinct antibody population in the same fractions reacted with a nerve terminal 65-kDa protein that is unrelated to the β subunit and displays properties similar to those of synaptotagmin. 相似文献
994.
Energy profile of maltooligosaccharide permeation through maltoporin as derived from the structure and from a statistical analysis of saccharide-protein interactions. 总被引:1,自引:0,他引:1 下载免费PDF全文
J. E. Meyer G. E. Schulz 《Protein science : a publication of the Protein Society》1997,6(5):1084-1091
The crystal structure of the maltodextrin-specific porin from Salmonella typhimurium ligated with a maltotrioside at the pore eyelet is known at 2.4 A resolution. The three glucose units assume a conformation close to the natural amylose helix. The pore eyelet fits exactly the cross-section of a maltooligosaccharide chain and thus functions as a constraining orifice. The oligomer permeates the membrane by screwing along the amylose helix through this orifice. Because each glucose glides along the given helix, its interactions can be sampled at any point along the pathway. The interactions are mostly hydrogen bonds, but also contacts to aromatic rings at one side of the pore. We have derived the energy profile of a gliding maltooligosaccharide by following formation and breakage of hydrogen bonds and by assessing the saccharide-aromatics interactions from a statistical analysis of saccharide binding sites in proteins. The resulting profile indicates smooth permeation despite extensive hydrogen bonding at the orifice. 相似文献
995.
Margreet E. Bossen Hans H. A. Dassen Richard E. Kendrick Willem J. Vredenberg 《Planta》1988,174(1):94-100
Protoplasts from dark-grown wheat (Triticum aestivum L.) maintained at a constant osmotic potential at 22°C, were found to swell upon red irradiation (R) and the effect was negated by subsequent far-red light (FR), indicating phytochrome involvement. Swelling only occurred when Ca2+ ions were present in the surrounding medium, or were added within 10 min after R. Furthermore, Mg2+, Ba2+ or K+ could not replace this requirement for Ca2+. The presence of K+ did not enhance the Ca2+-dependent swelling response. When the Ca2+-ionophore A 23187 was added to the medium, protoplasts swelled in the dark to the same extent as after R. Both the Ca2+-channelblocker Verapamil and La3+ inhibited R-induced swelling. It is proposed that R causes the opening of Ca2+-channels in the plasma membrane. Boyle-van't Hoff analyses of protoplast volume after R and FR are consistent with the conclusion that R irradiation causes changes in membrane properties.Abbreviations EDTA
ethylenediaminetetraacetic acid
- FR
far-red light
- nov
non-osmotic-volume
- Pfr
FR-absorbing form of phytochrome
- Pr
R-absorbing form of phytochrome
- R
red light 相似文献
996.
M. Z. Haque 《Plant and Soil》1988,109(1):31-36
Spikelet sterility induced by low temperature at the reproductive stage of rice increased further with the increase of nitrogen supply. Spikelet sterility in Fujisaka-5 did not increase due to low temperature when nitrogen supply was increased from 10 to 40 ppm and at 80 ppm nitrogen supply it was less affected than IR36. Total nitrogen content in the leaves increased with the increase of nitrogen supply and was forced to be associated with the spikelet sterility induced by low temperature. Based on auricle distance between the last two leaves, the most sensitive stage to low temperature damage differed in Fujisaka-5 and IR36. Spikelet sterility induced by low temperature for 10 days was very high in both the varieties and the effect of nitrogen was not clear.The effect of phosphorus on the spikelet sterility induced by low temperature at reproductive stage was not clear except that at the highest phosphorus (P) level (10 ppm) the spikelet sterility increased both in Fujisaka-5 and IR36.Spikelet sterility induced by low temperature at the reproductive stage of rice decreased with the increase of Potassium (K) supply in both Fujisaka-5 and IR36. With an increase of potassium supply, nitrogen (N) content decreased in the leaves and panicles and spikelet sterility induced by low temperature decreased with an increase of the K to N ratio in the leaves and panicles. The results suggest that potassium might play a major role to counteract the low temperature damage at the reproductive stage of rice. 相似文献
997.
《Molecular membrane biology》2013,30(3):133-145
In this paper, we describe a simple and reproducible method for purifying large quantities of ryanodine receptor from skeletal muscle membranes. The procedure involves the use of ion exchange chromatography and sucrose gradient centrifugation to purify the protein which has been identified as the calcium release protein of the sarcoplasmic reticulum (Imagawa, T., Smith, J., Coronado, R. and Campbell, K. (1987) J. Biol. Chem. 262:16,636–16,643). Addition of micromolar quantities of unlabeled ryanodine prior to solubilization and throughout the isolation procedure appears to stabilize the tetrameric structure of the ryanodine receptor. The purified receptor, consisting predominantly of a 400K polypeptide on SDS-PAGE, binds [3H]ryanodine with a binding affinity similar to that in membranes. Overall recovery of ryanodine binding activity was 21% of the initial activity with a 30-fold purification of the receptor. 相似文献
998.
Synaptic clusters on dendrites are extraordinarily compact computational building blocks. They contribute to key local computations through biophysical and biochemical signaling that utilizes convergence in space and time as an organizing principle. However, these computations can only arise in very special contexts. Dendritic cluster computations, their highly organized input connectivity, and the mechanisms for their formation are closely linked, yet these have not been analyzed as parts of a single process. Here, we examine these linkages. The sheer density of axonal and dendritic arborizations means that there are far more potential connections (close enough for a spine to reach an axon) than actual ones. We see how dendritic clusters draw upon electrical, chemical, and mechano–chemical signaling to implement the rules for formation of connections and subsequent computations. Crucially, the same mechanisms that underlie their functions also underlie their formation. 相似文献
999.
Summary This study is concerned with the short-circuit current,I
sc, responses of the Cl–-transporting cells of toad skin submitted to sudden changes of the external Cl– concentration. [Cl]0. Sudden changes of [Cl]0, carried out under apical membrane depolarization, allowed comparison of the roles of [Cl]0 and [Cl]cell on the activation of the apical Cl– pathways. Equilibration of shortcircuited skins symmetrically in K-Ringer's solutions of different Cl– concentrations permitted adjustment of [Cl]cell to different levels. For a given Cl– concentration (in the range of 11.7 to 117mm) on both sides of a depolarized apical membrane, this structure exhibits a high Cl– permeability,P
(Cl)apical. On the other hand, for the same range of [Cl]cell but with [Cl]0=0,P
(Cl)apical is reduced to negligible values. These observations indicate that when the apical membrane is depolarizedP
(Cl)apical is modulated by [Cl]0; in the absence of external Cl– ions, intracellular Cl– is not sufficient to activateP
(Cl)apical. Computer simulation shows that the fast Cl– currents induced across the apical membrane by sudden shifts of [Cl]0 from a control equilibrium value strictly follow the laws of electrodiffusion. For each experimental group, the computer-generatedI
sc
versus ([Cl]cell–[Cl]0) curve which best fits the experimental data can only be obtained by a unique pair ofP
(Cl)apical andR
b (resistance of the basolateral membrane), thus allowing the calculation of these parameters. The electrodiffusional behavior of the net Cl– flux across the apical membrane supports the channel nature of the apical Cl– pathways in the Cl–-transporting cell. Cl– ions contribute significantly to the overall conductance of the basolateral membrane even in the presence of a high K concentration in the internal solution. 相似文献
1000.
Gabriel St?lting Stefanie Bungert-Plümke Arne Franzen Christoph Fahlke 《The Journal of biological chemistry》2015,290(51):30406-30416
ClC-K chloride channels are crucial for auditory transduction and urine concentration. Mutations in CLCNKB, the gene encoding the renal chloride channel hClC-Kb, cause Bartter syndrome type III, a human genetic condition characterized by polyuria, hypokalemia, and alkalosis. In recent years, several Bartter syndrome-associated mutations have been described that result in truncations of the intracellular carboxyl terminus of hClC-Kb. We here used a combination of whole-cell patch clamp, confocal imaging, co-immunoprecipitation, and surface biotinylation to study the functional consequences of a frequent CLCNKB mutation that creates a premature stop codon at Trp-610. We found that W610X leaves the association of hClC-Kb and the accessory subunit barttin unaffected, but impairs its regulation by barttin. W610X attenuates hClC-Kb surface membrane insertion. Moreover, W610X results in hClC-Kb channel opening in the absence of barttin and prevents further barttin-mediated activation. To describe how the carboxyl terminus modifies the regulation by barttin we used V166E rClC-K1. V166E rClC-K1 is active without barttin and exhibits prominent, barttin-regulated voltage-dependent gating. Electrophysiological characterization of truncated V166E rClC-K1 demonstrated that the distal carboxyl terminus is necessary for slow cooperative gating. Since barttin modifies this particular gating process, channels lacking the distal carboxyl-terminal domain are no longer regulated by the accessory subunit. Our results demonstrate that the carboxyl terminus of hClC-Kb is not part of the binding site for barttin, but functionally modifies the interplay with barttin. The loss-of-activation of truncated hClC-Kb channels in heterologous expression systems fully explains the reduced basolateral chloride conductance in affected kidneys and the clinical symptoms of Bartter syndrome patients. 相似文献