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91.
Greiser JS Stross C Heinrich PC Behrmann I Hermanns HM 《The Journal of biological chemistry》2002,277(30):26959-26965
The glycoprotein 130 (gp130) is the common signal transducing receptor chain of the interleukin-6 family of cytokines. Here we investigated the requirements for transfer of the information given by ligand binding to the cytoplasmic domain of gp130. It is demonstrated that the box 1/2 region has to be located membrane-proximally in order to bind and activate Janus kinases. To test the possible requirement of an alpha-helical orientation, we inserted 1-4 alanine residues into this juxtamembrane intracellular region. The insertion of one alanine results in a strongly reduced activation of STAT1 and STAT3, whereas insertion of three alanine residues leads to a stronger STAT activation. These results suggest that gp130-mediated activation of STATs is sensitive to rotational changes around the receptor axis perpendicular to the membrane. Surprisingly, insertion of 1, 2, 3, or 4 alanine residues into this juxtamembrane region leads to successive impairment but not abolishment of Janus kinase and receptor phosphorylation, supporting the finding of sensitivity of Janus kinases toward changes in distance of box 1/2 from the plasma membrane. We suggest a new model concerning the gp130 activation mode in which the relative orientation of the cytoplasmic regions seems to be critical for further signal transduction. 相似文献
92.
Glutamine synthetase enhances the clearance of extracellular glutamate by the neural retina 总被引:4,自引:0,他引:4
Clearance of synaptic glutamate by glial cells is required for the normal function of excitatory synapses and for prevention of neurotoxicity. Although the regulatory role of glial glutamate transporters in glutamate clearance is well established, little is known about the influence of glial glutamate metabolism on this process. This study examines whether glutamine synthetase (GS), a glial-specific enzyme that amidates glutamate to glutamine, affects the uptake of glutamate. Retinal explants were incubated in the presence of [(14)C]glutamate and glutamate uptake was assessed by measurement of the amount of radioactively labeled molecules within the cells and the amount of [(14)C]glutamine released to the medium. An increase in GS expression in Müller glial cells, caused by induction of the endogenous gene, did not affect the amount of glutamate accumulated within the cells, but led to a dramatic increase in the amount of glutamine released. This increase, which was directly correlated with the level of GS expression, was dependent on the presence of external sodium ions, and could be completely abolished by methionine sulfoximine, a specific inhibitor of GS activity. Our results demonstrate that GS activity significantly influences the uptake of glutamate by the neural retina and suggest that this enzyme may represent an important target for neuroprotective strategies. 相似文献
93.
Coronatine-inducible tyrosine aminotransferase (TAT), which catalyses the transamination from tyrosine to p-hydroxyphenylpyruvate, is the first enzyme of a pathway leading via homogentisic acid to plastoquinone and tocopherols, the latter of which are known to be radical scavengers in plants. TAT can be also induced by the octadecanoids methyl jasmonate (MeJA) and methyl-12-oxophytodienoic acid (MeOPDA), as well as by wounding, high light, UV light and the herbicide oxyfluorfen. In order to elucidate the role of octadecanoids in the process of TAT induction in Arabidopsis thaliana (L.) Heynh., the jasmonate-deficient mutant delayed dehiscence (dde1) was used, in which the gene for 12-oxophytodienoic acid reductase 3 is disrupted. The amount of immunodetectable TAT was low. The enzyme was still fully induced by coronatine as well as by MeJA although induction by the latter was to a lesser extent and later than in the wild type. Treatment with MeOPDA, wounding and UV light, however, had hardly any effects. Tocopherol levels that showed considerable increases in the wild type after some treatments were much less affected in the mutant. However, starting levels of tocopherol were higher in non-induced dde1 than in the wild type. We conclude that jasmonate plays an important role in the signal transduction pathway regulating TAT activity and the biosynthesis of its product tocopherol. 相似文献
94.
Differential control of vesicle priming and short-term plasticity by Munc13 isoforms 总被引:21,自引:0,他引:21
Presynaptic short-term plasticity is an important adaptive mechanism regulating synaptic transmitter release at varying action potential frequencies. However, the underlying molecular mechanisms are unknown. We examined genetically defined and functionally unique axonal subpopulations of synapses in excitatory hippocampal neurons that utilize either Munc13-1 or Munc13-2 as synaptic vesicle priming factor. In contrast to Munc13-1-dependent synapses, Munc13-2-driven synapses show pronounced and transient augmentation of synaptic amplitudes following high-frequency stimulation. This augmentation is caused by a Ca(2+)-dependent increase in release probability and releasable vesicle pool size, and requires phospholipase C activity. Thus, differential expression of Munc13 isoforms at individual synapses represents a general mechanism that controls short-term plasticity and contributes to the heterogeneity of synaptic information coding. 相似文献
95.
During exploratory laparotomy, a 10-year-old female rhesus macaque was found to have a 6.0 x 9.5 x 2.0-cm multichambered, yellow, cystic mass cranial to the uterus, from which large amounts of opaque, white fluid were discharged into the abdominal cavity. The animal was euthanized, and the body was submitted for gross and histologic evaluation. Sections of the mass examined microscopically consisted of sheets of polygonal to round cells, with well defined cell borders and moderate amounts of eosinophilic cytoplasm. Scattered throughout these cells were few, variably sized glandular structures composed of columnar to cuboidal epithelium. Glandular epithelial cells were positive for keratin, and the sheets of polygonal cells were positive for vimentin and negative for keratin and CD 68. Gross and histologic appearance, immunohistochemical findings, and history of medroxyprogesterone acetate injections were compatible with a diagnosis of stromal decidualization of endometriosis. Subsequent biopsies of similar lesions in other rhesus macaques in the colony being treated with medroxyprogesterone acetate for endometriosis revealed comparable histologic findings. 相似文献
96.
bicoid (bcd) RNA localization requires the activity of exuperantia and swallow at sequential steps of oogenesis and is microtubule dependent. In a genetic screen, we identified two novel genes essential for bcd RNA localization. They encode maternal gamma-Tubulin37C (gammaTub37C) and gamma-tubulin ring complex protein 75 (Dgrip75), both of which are gamma-tubulin ring complex components. Mutations in these genes specifically affect bcd RNA localization, whereas other microtubule-dependent processes during oogenesis are not impaired. This provides direct evidence that a subset of microtubules organized by the gamma-tubulin ring complex is essential for localization of bcd RNA. At stage 10b, we find gammaTub37C and Dgrip75 anteriorly concentrated and propose the formation of a microtubule-organizing center at the anterior pole of the oocyte. 相似文献
97.
Zimmermann P Meerschaert K Reekmans G Leenaerts I Small JV Vandekerckhove J David G Gettemans J 《Molecular cell》2002,9(6):1215-1225
PDZ proteins organize multiprotein signaling complexes. According to current views, PDZ domains engage in protein-protein interactions. Here we show that the PDZ domains of several proteins bind phosphatidylinositol 4,5-bisphosphate (PIP(2)). High-affinity binding of syntenin to PIP(2)-containing lipid layers requires both PDZ domains of this protein. Competition and mutagenesis experiments reveal that the protein and the PIP(2) binding sites in the PDZ domains overlap. Overlay assays indicate that the two PDZ domains of syntenin cooperate in binding to cognate peptides and PIP(2). Experiments on living cells demonstrate PIP(2)-dependent and peptide-dependent modes of plasma membrane association of the PDZ domains of syntenin. These observations suggest that local changes in phosphoinositide concentration control the association of PDZ proteins with their target receptors at the plasma membrane. 相似文献
98.
Boll W Rapoport I Brunner C Modis Y Prehn S Kirchhausen T 《Traffic (Copenhagen, Denmark)》2002,3(8):590-600
The endocytic sorting signal on the low-density lipoprotein receptor for clathrin-mediated internalization is the sequence FDNPVY in the receptor's cytosolic tail. We have used a combination of surface plasmon resonance and crosslinking with a photoactivated peptide probe to demonstrate the interaction between FDNPVY-containing peptides and the μ2 chain of purified AP-2 clathrin adaptors (the complexes responsible for plasma membrane sorting). We show that recognition of the FDNPVY signal is mediated by a binding site in the μ2-subunit that is distinct from the site for the more general YppØ sorting signal, another tyrosine-based sequence also recognized by μ2-adaptin. These results suggest the possibility that low-density lipoprotein receptor uptake may be modulated specifically and independently of other proteins in the clathrin pathway. 相似文献
99.
Iris Menn 《Helgoland Marine Research》2002,56(3):177-189
Food web components and inorganic nutrients were studied on two sandy shores of the adjacent barrier islands of Sylt and
R?m? in the North Sea, differing in morphodynamics. Implications of high and low wave energy on the food web structure were
assessed. The Sylt shore represents a dynamic intermediate beach type, while the R?m? shore is morphologically stable and
dissipative. On the steep-profiled, coarse-grained Sylt shore, strong hydrodynamics resulted in erosion and high fluxes of
organic material through the beach, but prevented any storage of food sources. In contrast, the flat-profiled, fine-grained
R?m? shore, with low wave energy and accretion, accumulated organic carbon from surf waters. At Sylt, oxic nutrient regeneration
prevailed, while anoxic mineralization was more important at R?m?. Macrofauna on the Sylt shore was impoverished compared
with the community at R?m?. Correspondingly, abundances of epibenthic predators such as shrimps, crabs, fish, and shorebirds
were also lower at Sylt. Meiofauna was abundant on both shores, but differed in taxonomic composition. Several major taxa
were represented in fairly equal proportions of individual numbers on the well-oxygenated Sylt shore, while nematodes strongly
dominated the assemblage at R?m?. Thus, on cold-temperate, highly dynamic intermediate shores with high wave energy and subject
to erosion, the "small food web" dominates. Organisms are agile and quickly exploit fresh organic material. Larger organisms
and nematodes abound under stable, dissipative and accreting shore conditions, where some food materials may accumulate and
zoomass builds up to support numerous visitors from higher trophic levels.
Electronic Publication 相似文献
100.
Photoactive yellow protein (PYP) is a prototype of the PAS domain superfamily of signaling proteins. The signaling process
is coupled to a three-state photocycle. After the photoinduced trans-cis isomerization of the chromophore, 4-hydroxycinnamic acid (pCA), an early intermediate (pR) is formed, which proceeds to a
second intermediate state (pB) on a sub-millisecond time scale. The signaling process is thought to be connected to the conformational
changes upon the formation of pB and its recovery to the ground state (pG), but the exact signaling mechanism is not known.
Experimental studies of PYP by solution NMR and X-ray crystallography suggest a very flexible protein backbone in the ground
as well as in the signaling state. The relaxation from the pR to the pB state is accompanied by the protonation of the chromophore's
phenoxyl group. This was found to be of crucial importance for the relaxation process. With the goal of gaining a better understanding
of these experimental observations on an atomistic level, we performed five MD simulations on the three different states of
PYP: a 1 ns simulation of PYP in its ground state [pG(MD)], a 1 ns simulation of the pR state [pR(MD)], a 2 ns simulation
of the pR state with the chromophore protonated (pRprot), a 2 ns simulation of the pR state with Glu46 exchanged by Gln (pRGln)
and a 2 ns simulation of PYP in its signaling state [pB(MD)]. Comparison of the pG simulation results with X-ray and NMR data,
and with the results obtained for the pB simulation, confirmed the experimental observations of a rather flexible protein
backbone and conformational changes during the recovery of the pG from the pB state. The conformational changes in the region
around the chromophore pocket in the pR state were found to be crucially dependent on the strength of the Glu46-pCA hydrogen
bond, which restricts the mobility of the chromophore in its unprotonated form considerably. Both the mutation of Glu46 with
Gln and the protonation of the chromophore weaken this hydrogen bond, leading to an increased mobility of pCA and large structural
changes in its surroundings. These changes, however, differ considerably during the pRGln and pRprot simulations, providing
an atomistic explanation for the enhancement of the rate constant in the Gln46 mutant.
Electronic supplementary material to this article is available at and is accessible for athorized users.
Electronic Publication 相似文献