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排序方式: 共有266条查询结果,搜索用时 265 毫秒
91.
Hans-Michael Müller Julia P. Steringer Sabine Wegehingel Stephanie Bleicken Maximilian Münster Eleni Dimou Sebastian Unger Georg Weidmann Helena Andreas Ana J. García-Sáez Klemens Wild Irmgard Sinning Walter Nickel 《The Journal of biological chemistry》2015,290(14):8925-8937
Fibroblast growth factor 2 (FGF2) is a key signaling molecule in tumor-induced angiogenesis. FGF2 is secreted by an unconventional secretory mechanism that involves phosphatidylinositol 4,5-bisphosphate-dependent insertion of FGF2 oligomers into the plasma membrane. This process is regulated by Tec kinase-mediated tyrosine phosphorylation of FGF2. Molecular interactions driving FGF2 monomers into membrane-inserted FGF2 oligomers are unknown. Here we identify two surface cysteines that are critical for efficient unconventional secretion of FGF2. They represent unique features of FGF2 as they are absent from all signal-peptide-containing members of the FGF protein family. We show that phosphatidylinositol 4,5-bisphosphate-dependent FGF2 oligomerization concomitant with the generation of membrane pores depends on FGF2 surface cysteines as either chemical alkylation or substitution with alanines impairs these processes. We further demonstrate that the FGF2 variant forms lacking the two surface cysteines are not secreted from cells. These findings were corroborated by experiments redirecting a signal-peptide-containing FGF family member from the endoplasmic reticulum/Golgi-dependent secretory pathway into the unconventional secretory pathway of FGF2. Cis elements known to be required for unconventional secretion of FGF2, including the two surface cysteines, were transplanted into a variant form of FGF4 without signal peptide. The resulting FGF4/2 hybrid protein was secreted by unconventional means. We propose that the formation of disulfide bridges drives membrane insertion of FGF2 oligomers as intermediates in unconventional secretion of FGF2. 相似文献
92.
Small-scale spatial variability in phylogenetic community structure during early plant succession depends on soil properties 总被引:1,自引:0,他引:1
Werner Ulrich Marcin Piwczyński Markus Klemens Zaplata Susanne Winter Wolfgang Schaaf Anton Fischer 《Oecologia》2014,175(3):985-995
During early plant succession, the phylogenetic structure of a community changes in response to important environmental filters and emerging species interactions. We traced the development of temperate-zone plant communities during the first 7 years of primary succession on catchment soils to explore patterns of initial species assembly. We found pronounced small-scale differences in the phylogenetic composition of neighbouring plant assemblages and a large-scale trend towards phylogenetic evenness. This small-scale variability appears to be mediated by soil properties, particularly carbonate content. Therefore, abiotic environmental conditions might counteract or even supersede the effects of interspecific competition among closely related species, which are usually predicted to exhibit patterns of phylogenetic evenness. We conclude that theories on phylogenetic community composition need to incorporate effects of small-scale variability of environmental factors. 相似文献
93.
Background
B cells and humoral immune responses play an important role in the pathogenesis and diagnosis of multiple sclerosis (MS). A characteristic finding in patients with MS is a polyspecific intrathecal B cell response against neurotropic viruses, specifically against measles virus, rubella virus, and varicella zoster virus, also known as an MRZ reaction (MRZR). Here, we correlated from the routine clinical diagnostics individual IgG antibody indices (AIs) of MRZR with magnetic resonance imaging (MRI) findings in patients with first MS diagnosis.Methods/Results
MRZR was determined in 68 patients with a clinically isolated syndrome (CIS) or early relapsing-remitting MS (RRMS). Absolute AI values for measles virus, rubella virus, and varicella zoster virus were correlated with T2 lesion load and gadolinium enhancing lesions on cerebral MRI (cMRI) and cMRI combined with spinal MRI (sMRI). Measles virus AI correlated significantly with T2 lesion load on cMRI (p = 0.0312, Mann-Whitney U test) and the sum of lesions on cMRI and sMRI (p = 0.0413). Varicella zoster virus AI also showed a correlation with T2 lesion load on cMRI but did not reach statistical significance (p = 0.2893).Conclusion
The results confirm MRZR as part of the polyspecific immune reaction in MS with possible prognostic impact on MRI and clinical parameters.Furthermore, the data indicate that intrathecal measles virus IgG production correlates with disease activity on cMRI and sMRI in patients with early MS. 相似文献94.
Els?M.?van der?ZeeEmail author Tjisse?van der?Heide Serena?Donadi Johan?S.?Ekl?f Britas?Klemens?Eriksson Han?Olff Henk?W.?van der?Veer Theunis?Piersma 《Ecosystems》2012,15(4):664-673
Ecosystem engineers can strongly modify habitat structure and resource availability across space. In theory, this should alter
the spatial distributions of trophically interacting species. In this article, we empirically investigated the importance
of spatially extended habitat modification by reef-building bivalves in explaining the distribution of four avian predators
and their benthic prey in the Wadden Sea—one of the world’s largest intertidal soft-sediment ecosystems. We applied Structural
Equation Modeling to identify important direct and indirect interactions between the different components of the system. We
found strong spatial gradients in sediment properties into the surrounding area of mixed blue mussel (Mytilus edulis) and Pacific oyster (Crassostrea gigas) reefs, indicating large-scale (100s of m) engineering effects. The benthic community was significantly affected by these
gradients, with the abundance of several important invertebrate prey species increasing with sediment organic matter and decreasing
with distance to the reefs. Distance from the reef, sediment properties, and benthic food abundance simultaneously explained
significant parts of the distribution of oystercatchers (Haematopus ostralegus), Eurasian curlews (Numenius arquata), and bar-tailed godwits (Limosa lapponica). The distribution of black-headed gulls (Chroicocephalus ridibundus)—a versatile species with many diet options—appeared unaffected by the reefs. These results suggest that intertidal reef
builders can affect consumer-resource dynamics far beyond their own boundaries, emphasizing their importance in intertidal
soft-bottom ecosystems like the Wadden Sea. 相似文献
95.
96.
Halabi-Cabezon I Huelsenbeck J May M Ladwein M Rottner K Just I Genth H 《FEBS letters》2008,582(27):3751-3756
Clostridium difficile Toxin B (TcdB) glucosylates low molecular weight GTP-binding proteins of the Rho subfamily and thereby causes actin re-organization (cell rounding). This "cytopathic effect" has been generally attributed to RhoA inactivation. Here we show that cells expressing non-glucosylatable Rac1-Q61L are protected from the cytopathic effect of TcdB. In contrast, cells expressing RhoA-Q63L or mock-transfected cells are fully susceptible for the cytopathic effect of TcdB. These findings are extended to the Rac1/RhoG mimic IpgB1 and the RhoA mimic IpgB2 from Shigella. Ectopic expression of IpgB1, but not IpgB2, counteracts the cytopathic effect of TcdB. These data strongly suggest that Rac1 rather than RhoA glucosylation is critical for the cytopathic effect of TcdB. 相似文献
97.
Lai FP Szczodrak M Block J Faix J Breitsprecher D Mannherz HG Stradal TE Dunn GA Small JV Rottner K 《The EMBO journal》2008,27(7):982-992
Cell migration is initiated by lamellipodia-membrane-enclosed sheets of cytoplasm containing densely packed actin filament networks. Although the molecular details of network turnover remain obscure, recent work points towards key roles in filament nucleation for Arp2/3 complex and its activator WAVE complex. Here, we combine fluorescence recovery after photobleaching (FRAP) of different lamellipodial components with a new method of data analysis to shed light on the dynamics of actin assembly/disassembly. We show that Arp2/3 complex is incorporated into the network exclusively at the lamellipodium tip, like actin, at sites coincident with WAVE complex accumulation. Capping protein likewise showed a turnover similar to actin and Arp2/3 complex, but was confined to the tip. In contrast, cortactin-another prominent Arp2/3 complex regulator-and ADF/cofilin-previously implicated in driving both filament nucleation and disassembly-were rapidly exchanged throughout the lamellipodium. These results suggest that Arp2/3- and WAVE complex-driven actin filament nucleation at the lamellipodium tip is uncoupled from the activities of both cortactin and cofilin. Network turnover is additionally regulated by the spatially segregated activities of capping protein at the tip and cofilin throughout the mesh. 相似文献
98.
Field and laboratory research has repeatedly shown that free-living soil nematodes differ in their sensitivity to soil pollution. In this paper, we analyze whether nematode genera proved sensitive or tolerant toward heavy metals and organic pollutants in six long-term field experiments. We discuss overlaps between nematode physiological responses to heavy metals and to organic pollutants, which may explain why nematodes can exhibit co-tolerance toward several contaminants. We propose a simple method for separating direct effects of soil contamination on nematode populations from indirect effects mediated through the food chain. Finally, we analyze the extent to which nematodes exhibited consistent responses across the experiments analyzed. Our results show that (a) indirect effects of pollution were generally strong; (b) fewer nematode genera were tolerant than sensitive; (c) many genera, including practically all Adenophorea, exhibited a common response pattern to contaminants; and (d) several genera of the Secernentea exhibited differential tolerance toward particular pollutants. We conclude that bioindication of soil contamination should preferentially be based on tolerant, and less on sensitive, nematodes. We provide a list of nematode genera that may potentially serve as differential bioindicators for specific soil contaminants. 相似文献
99.
MT1-MMP-dependent invasion is regulated by TI-VAMP/VAMP7 总被引:1,自引:0,他引:1
Steffen A Le Dez G Poincloux R Recchi C Nassoy P Rottner K Galli T Chavrier P 《Current biology : CB》2008,18(12):926-931
Proteolytic degradation of the extracellular matrix (ECM) is one intrinsic property of metastatic tumor cells to breach tissue barriers and to disseminate into different tissues. This process is initiated by the formation of invadopodia, which are actin-driven, finger-like membrane protrusions. Yet, little is known on how invadopodia are endowed with the functional machinery of proteolytic enzymes [1, 2]. The key protease MT1-MMP (membrane type 1-matrix metalloproteinase) confers proteolytic activity to invadopodia and thus invasion capacity of cancer cells [3-6]. Here, we report that MT1-MMP-dependent matrix degradation at invadopodia is regulated by the v-SNARE TI-VAMP/VAMP7, hence providing the molecular inventory mediating focal degradative activity of cancer cells. As observed by TIRF microscopy, MT1-MMP-mCherry and GFP-VAMP7 were simultaneously detected at proteolytic sites. Functional ablation of VAMP7 decreased the ability of breast cancer cells to degrade and invade in a MT1-MMP-dependent fashion. Moreover, the number of invadopodia was dramatically decreased in VAMP7- and MT1-MMP-depleted cells, indicative of a positive-feedback loop in which the protease as a cargo of VAMP7-targeted transport vesicles regulates maturation of invadopodia. Collectively, these data point to a specific role of VAMP7 in delivering MT1-MMP to sites of degradation, maintaining the functional machinery required for invasion. 相似文献
100.