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排序方式: 共有628条查询结果,搜索用时 31 毫秒
61.
Tariq Butt Tabish Mufti Ahmad Humayun Peter B. Rosenthal Sohaib Khan Shahid Khan Justin E. Molloy 《The Journal of biological chemistry》2010,285(7):4964-4974
The bulk alignment of actin filament sliding movement, powered by randomly oriented myosin molecules, has been observed and studied using an in vitro motility assay. The well established, actin filament gliding assay is a minimal experimental system for studying actomyosin motility. Here, we show that when the assay is performed at densities of actin filaments approaching those found in living cells, filament gliding takes up a preferred orientation. The oriented patterns of movement that we have observed extend over a length scale of 10–100 μm, similar to the size of a mammalian cell. We studied the process of filament alignment and found that it depends critically upon filament length and density. We developed a simple quantitative measure of filament sliding orientation and this enabled us to follow the time course of alignment and the formation and disappearance of oriented domains. Domains of oriented filaments formed spontaneously and were separated by distinct boundaries. The pattern of the domain structures changed on the time scale of several seconds and the collision of neighboring domains led to emergence of new patterns. Our results indicate that actin filament crowding may play an important role in structuring the leading edge of migrating cells. Filament alignment due to near-neighbor mechanical interactions can propagate over a length scale of several microns; much greater than the size of individual filaments and analogous to a log drive. Self-alignment of actin filaments may make an important contribution to cell polarity and provide a mechanism by which cell migration direction responds to chemical cues. 相似文献
62.
Hibbert JE Butt RH Coorssen JR 《The international journal of biochemistry & cell biology》2006,38(3):461-471
Actin has been suggested as an essential component in the membrane fusion stage of exocytosis. In some model systems disruption of the actin filament network associated with exocytotic membranes results in a decrease in secretion. Here we analyze the fast Ca2+-triggered membrane fusion steps of regulated exocytosis using a stage-specific preparation of native secretory vesicles (SV) to directly test whether actin plays an essential role in this mechanism. Although present on secretory vesicles, selective pharmacological inhibition of actin did not affect the Ca2+-sensitivity, extent, or kinetics of membrane fusion, nor did the addition of exogenous actin or an anti-actin antibody. There was also no discernable affect on inter-vesicle contact (docking). Overall, the results do not support a direct role for actin in the fast, Ca2+-triggered steps of regulated membrane fusion. It would appear that actin acts elsewhere within the exocytotic cycle. 相似文献
63.
Gambaryan S Butt E Tas P Smolenski A Allolio B Walter U 《American journal of physiology. Endocrinology and metabolism》2006,290(3):E423-E433
Aldosterone production in zona glomerulosa (ZG) cells of adrenal glands is regulated by various extracellular stimuli (K(+), ANG II, ACTH) that all converge on two major intracellular signaling pathways: an increase in cAMP production and calcium (Ca(2+)) mobilization. However, molecular events downstream of the increase in intracellular cAMP and Ca(2+) content are controversial and far from being completely resolved. Here, we found that Ca(2+)/calmodulin-dependent protein kinases (CaMKs) play a predominant role in the regulation of aldosterone production stimulated by ANG II, ACTH, and cAMP. The specific CaMK inhibitor KN93 strongly reduced ANG II-, ACTH-, and cAMP-stimulated aldosterone production. In in vitro kinase assays and intact cells, we could show that cAMP-induced activation of CaMK, using the adenylate cyclase activator forskolin or the cAMP-analog Sp-5,6-DCI-cBIMPS (cBIMPS), was not mediated by PKA. Activation of the recently identified cAMP target protein Epac (exchange protein directly activated by cAMP) by 8-pCPT-2'-O-Me-cAMP had no effect on CaMK activity and aldosterone production. Furthermore, we provide evidence that cAMP effects in ZG cells do not involve Ca(2+) or MAPK signaling. Our results suggest that ZG cells, in addition to PKA and Epac/Rap proteins, contain other as yet unidentified cAMP mediator(s) involved in regulating CaMK activity and aldosterone secretion. 相似文献
64.
McMillan DG Marritt SJ Butt JN Jeuken LJ 《The Journal of biological chemistry》2012,287(17):14215-14225
Little is known about enzymatic quinone-quinol interconversions in the lipid membrane when compared with our knowledge of substrate transformations by globular enzymes. Here, the smallest example of a quinol dehydrogenase in nature, CymA, has been studied. CymA is a monotopic membrane tetraheme c-type cytochrome belonging to the NapC/NirT family and central to anaerobic respiration in Shewanella sp. Using protein-film electrochemistry, it is shown that vesicle-bound menaquinone-7 is not only a substrate for this enzyme but is also required as a cofactor when converting other quinones. Here, we propose that the high concentration of quinones in the membrane negates the evolutionary pressure to create a high affinity active site. However, the instability and reactivity of reaction intermediate, semiquinone, might require a cofactor that functions to minimize damaging side reactions. 相似文献
65.
The precise characterization of post translational modifications (PTMs) is important for the understanding of protein regulatory
mechanisms and their role in disease. However, experimental studies on PTMs, especially with multifunctional proteins are
difficult to follow and investigate. Bioinformatic tools are therefore helpful in predicting key protein modifications. To
study the role of PTMs in claudin proteins, specifically claudin-1, -3 and -4 in the onset or progression of human cancers,
we performed an in silico study of various PTMs and investigated their interplay. Given that the activity of claudins is known
to be influenced by two types of PTMs, specifically palmitoylation and kinase- dependent phosphorylation, we predicted two
conserved regions in the topological domains of claudin-1, -3 and -4 as potential palmitoylation sites. Furthermore, conserved
phosphorylation residues, which may be targets for kinases and can alter claudin’s ability to maintain the integrity of tight
junctions, were identified. To our knowledge, this is the first report to suggest O-glycosylation of claudin proteins, as well as a potential novel interplay between phosphorylation and O-glycosylation at Yin Yang sites. Thus, our findings may facilitate the production of anti-cancer drugs, and suggest that
novel therapeutic strategies should target post translational events. 相似文献
66.
67.
Richardson DJ Edwards MJ White GF Baiden N Hartshorne RS Fredrickson J Shi L Zachara J Gates AJ Butt JN Clarke TA 《Biochemical Society transactions》2012,40(3):493-500
Many species of the bacterial Shewanella genus are notable for their ability to respire in anoxic environments utilizing insoluble minerals of Fe(III) and Mn(IV) as extracellular electron acceptors. In Shewanella oneidensis, the process is dependent on the decahaem electron-transport proteins that lie at the extracellular face of the outer membrane where they can contact the insoluble mineral substrates. These extracellular proteins are charged with electrons provided by an inter-membrane electron-transfer pathway that links the extracellular face of the outer membrane with the inner cytoplasmic membrane and thereby intracellular electron sources. In the present paper, we consider the common structural features of two of these outer-membrane decahaem cytochromes, MtrC and MtrF, and bring this together with biochemical, spectroscopic and voltammetric data to identify common and distinct properties of these prototypical members of different clades of the outer-membrane decahaem cytochrome superfamily. 相似文献
68.
69.
Justin M. Bradley Sophie J. Marritt Margaret A. Kihlken Kate Haynes Andrew M. Hemmings Ben C. Berks Myles R. Cheesman Julea N. Butt 《The Journal of biological chemistry》2012,287(48):40350-40359
SoxAX enzymes couple disulfide bond formation to the reduction of cytochrome c in the first step of the phylogenetically widespread Sox microbial sulfur oxidation pathway. Rhodovulum sulfidophilum SoxAX contains three hemes. An electrochemical cell compatible with magnetic circular dichroism at near infrared wavelengths has been developed to resolve redox and chemical properties of the SoxAX hemes. In combination with potentiometric titrations monitored by electronic absorbance and EPR, this method defines midpoint potentials (Em) at pH 7.0 of approximately +210, −340, and −400 mV for the His/Met, His/Cys−, and active site His/CysS−-ligated heme, respectively. Exposing SoxAX to S2O42−, a substrate analog with Em ∼−450 mV, but not Eu(II) complexed with diethylene triamine pentaacetic acid (Em ∼−1140 mV), allows cyanide to displace the cysteine persulfide (CysS−) ligand to the active site heme. This provides the first evidence for the dissociation of CysS− that has been proposed as a key event in SoxAX catalysis. 相似文献
70.