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61.
The processing of pre-mRNAs is a fundamental step required for the expression of most metazoan genes. Members of the family
of serine/arginine (SR)-rich proteins are critical components of the machineries carrying out these essential processing events,
highlighting their importance in maintaining efficient gene expression. SR proteins are characterized by their ability to
interact simultaneously with RNA and other protein components via an RNA recognition motif (RRM) and through a domain rich
in arginine and serine residues, the RS domain. Their functional roles in gene expression are surprisingly diverse, ranging
from their classical involvement in constitutive and alternative pre-mRNA splicing to various post-splicing activities, including
mRNA nuclear export, nonsense-mediated decay, and mRNA translation. These activities point up the importance of SR proteins
during the regulation of mRNA metabolism. 相似文献
62.
Maud Hertzog Francesca Milanesi Larnele Hazelwood Andrea Disanza HongJun Liu Emilie Perlade Maria Grazia Malabarba Sebastiano Pasqualato Alessio Maiolica Stefano Confalonieri Christophe Le Clainche Nina Offenhauser Jennifer Block Klemens Rottner Pier Paolo Di Fiore Marie-France Carlier Niels Volkmann Dorit Hanein Giorgio Scita 《PLoS biology》2010,8(6)
Actin capping and cross-linking proteins regulate the dynamics and architectures
of different cellular protrusions. Eps8 is the founding member of a unique
family of capping proteins capable of side-binding and bundling actin filaments.
However, the structural basis through which Eps8 exerts these functions remains
elusive. Here, we combined biochemical, molecular, and genetic approaches with
electron microscopy and image analysis to dissect the molecular mechanism
responsible for the distinct activities of Eps8. We propose that bundling
activity of Eps8 is mainly mediated by a compact four helix bundle, which is
contacting three actin subunits along the filament. The capping activity is
mainly mediated by a amphipathic helix that binds within the hydrophobic pocket
at the barbed ends of actin blocking further addition of actin monomers.
Single-point mutagenesis validated these modes of binding, permitting us to
dissect Eps8 capping from bundling activity in vitro. We further showed that the
capping and bundling activities of Eps8 can be fully dissected in vivo,
demonstrating the physiological relevance of the identified Eps8
structural/functional modules. Eps8 controls actin-based motility through its
capping activity, while, as a bundler, is essential for proper intestinal
morphogenesis of developing Caenorhabditis elegans. 相似文献
63.
Anita G. Jung Christina Labarerra Anna M. Jansen Klaus Qvortrup Klemens Wild Ole Kjaerulff 《PloS one》2010,5(3)
Background
Endophilin is a cytoplasmic protein with an important function in clathrin-dependent endocytosis at synapses and elsewhere. Endophilin has a BAR (Bin/Amphiphysin/Rvs-homology) domain, which is implicated in the sensing and induction of membrane curvature. Previous structure-function studies of the endophilin-A BAR domain have almost exclusively been made in reduced systems, either in vitro or ex vivo in cultured cells. To extend and complement this work, we have analyzed the role played by the structural features of the endophilin-A BAR domain in Drosophila in vivo.Methodology/Principal Findings
The study is based on genetic rescue of endophilin-A (endoA) null mutants with wild type or mutated endoA transgenes. We evaluated the viability of the rescuants, the locomotor behavior in adult flies and the neurotransmission at the larval neuromuscular junction. Whereas mutating the endophilin BAR domain clearly affected adult flies, larval endophilin function was surprisingly resistant to mutagenesis. Previous reports have stressed the importance of a central appendage on the convex BAR surface, which forms a hydrophobic ridge able to directly insert into the lipid bilayer. We found that the charge-negative substitution A66D, which targets the hydrophobic ridge and was reported to completely disrupt the ability of endophilin-BAR to tubulate liposomes in vitro, rescued viability and neurotransmission with the same efficiency as wild type endoA transgenes, even in adults. A similar discrepancy was found for the hydrophilic substitutions A63S/A66S and A63S/A66S/M70Q. The A66W mutation, which introduces a bulky hydrophobic side chain and induces massive vesiculation of liposomes in vitro, strongly impeded eye development, even in presence of the endogenous endoA gene. Substantial residual function was observed in larvae rescued with the EndoA(Arf) transgene, which encodes a form of endophilin-A that completely lacks the central appendage. Whereas a mutation (D151P) designed to increase the BAR curvature was functional, another mutation (P143A, ΔLEN) designed to decrease the curvature was not.Conclusions/Significance
Our results provide novel insight into the structure/function relationship of the endophilin-A BAR domain in vivo, especially with relation to synaptic function. 相似文献64.
Cyclosporine A (CsA)-induced glomerulosclerosis is a well-described side effect of CsA treatment. Current evidence indicates that FK506 causes similar morphologic changes. Recently, we demonstrated that CsA up-regulates the expression of transforming growth factor-beta1 (TGF-beta1), its receptors type I (TbetaR-I) and type II (TbetaR-II), as well as related matrix protein synthesis in mesangial cells (MCs). Here, we assessed the effect of FK506 on the expression of TGF-beta1, TbetaR-I, TbetaR-II, fibronectin (FN) and plasminogen activator inhibitor type-1 (PAI-1) in MCs. Resting MCs were incubated with/without FK506. Time- and concentration-dependent expression was measured at the mRNA and protein level. Compared to untreated controls, FK506 stimulated TGF-beta1 mRNA (maximum at 8 h, 100 ng/mL: 2.13+/-0.15-fold, P<0.005) and protein expression (maximum at 96 h, 100 ng/mL: 1.96+/-0.29-fold, P<0.005). In contrast, TbetaR-I and TbetaR-II protein expression remained unchanged. Concerning matrix protein synthesis, FK506 slightly increased FN production (96 h, 100 ng/mL: 1.38+/-0.28-fold, P<0.05), but not PAI-1 production. These results indicate that, comparable to CsA, FK506 induced glomerulosclerosis is also due to a direct effect on mesangial matrix production, which is at least in part mediated via up-regulation of TGF-beta1 expression. The fact that, unlike CsA, FK506 does not increase the expression of TbetaR-I, TbetaR-II, and PAI-1, deserves further investigation. 相似文献
65.
Steffen A Faix J Resch GP Linkner J Wehland J Small JV Rottner K Stradal TE 《Molecular biology of the cell》2006,17(6):2581-2591
Cell migration is initiated by plasma membrane protrusions, in the form of lamellipodia and filopodia. The latter rod-like projections may exert sensory functions and are found in organisms as distant in evolution as mammals and amoeba such as Dictyostelium discoideum. In mammals, lamellipodia protrusion downstream of the small GTPase Rac1 requires a multimeric protein assembly, the WAVE-complex, which activates Arp2/3-mediated actin filament nucleation and actin network assembly. A current model of filopodia formation postulates that these structures arise from a dendritic network of lamellipodial actin filaments by selective elongation and bundling. Here, we have analyzed filopodia formation in mammalian cells abrogated in expression of essential components of the lamellipodial actin polymerization machinery. Cells depleted of the WAVE-complex component Nck-associated protein 1 (Nap1), and, in consequence, of lamellipodia, exhibited normal filopodia protrusion. Likewise, the Arp2/3-complex, which is essential for lamellipodia protrusion, is dispensable for filopodia formation. Moreover, genetic disruption of nap1 or the WAVE-orthologue suppressor of cAMP receptor (scar) in Dictyostelium was also ineffective in preventing filopodia protrusion. These data suggest that the molecular mechanism of filopodia formation is conserved throughout evolution from Dictyostelium to mammals and show that lamellipodia and filopodia formation are functionally separable. 相似文献
66.
67.
Wild K Weichenrieder O Strub K Sinning I Cusack S 《Current opinion in structural biology》2002,12(1):72-81
The signal recognition particle (SRP) is a ubiquitous ribonucleoprotein particle involved in the co-translational targeting of proteins to membranes. Crystal structures are now available for three protein-RNA subcomplexes from the SRP, which give insights into fundamental aspects of protein-RNA recognition, the assembly of stable ribonucleoprotein particles and the mechanism of action of the SRP. 相似文献
68.
Klemens Pütz Jeremy G. Smith Rebecca J. Ingham Bernhard H. Lüthi 《Journal of avian biology》2003,34(2):139-144
The foraging patterns of ten male rockhopper penguins Eudyptes chrysocome from the Falkland Islands were recorded during the incubation period by using satellite telemetry. Irrespective of study site and year, two different foraging areas could be identified. Three foraging trips were directed towards the slope of the Patagonian Shelf c. 140 km to the northeast of the breeding colony and these trips had a duration of 11–15 days. The seven other rockhopper penguins travelled c. 400 km towards the edge of the Falkland Islands' waters; all these foraging trips followed an anti-clockwise direction and lasted 16–27 days. The calculated mean daily travelling speed, based on the time spent underwater and the distance covered between two positions, was significantly higher in birds travelling to the edge of the Falkland Islands' waters compared with those foraging at the shelf slope (4.4±1.6 km/h vs. 3.4±2.0 km/h, respectively). The consistent foraging patterns exhibited during the long trips may be linked to the Falklands current, allowing the penguins to reach remote areas while reducing their energy expenditure. Potential interactions between commercial fisheries and hydrocarbon exploration are discussed. 相似文献
69.
Cara-Paige Green David B. Green Norman Ratcliffe David Thompson Mary-Anne Lea Alastair M. M. Baylis Alexander L. Bond Charles-André Bost Sarah Crofts Richard J. Cuthbert Jacob González-Solís Kyle W. Morrison Maud Poisbleau Klemens Pütz Andrea Raya Rey Peter G. Ryan Paul M. Sagar Antje Steinfurth Jean-Baptiste Thiebot Megan Tierney Thomas Otto Whitehead Simon Wotherspoon Mark A. Hindell 《Global Change Biology》2023,29(3):648-667
Anthropogenic climate change is resulting in spatial redistributions of many species. We assessed the potential effects of climate change on an abundant and widely distributed group of diving birds, Eudyptes penguins, which are the main avian consumers in the Southern Ocean in terms of biomass consumption. Despite their abundance, several of these species have undergone population declines over the past century, potentially due to changing oceanography and prey availability over the important winter months. We used light-based geolocation tracking data for 485 individuals deployed between 2006 and 2020 across 10 of the major breeding locations for five taxa of Eudyptes penguins. We used boosted regression tree modelling to quantify post-moult habitat preference for southern rockhopper (E. chrysocome), eastern rockhopper (E. filholi), northern rockhopper (E. moseleyi) and macaroni/royal (E. chrysolophus and E. schlegeli) penguins. We then modelled their redistribution under two climate change scenarios, representative concentration pathways RCP4.5 and RCP8.5 (for the end of the century, 2071–2100). As climate forcings differ regionally, we quantified redistribution in the Atlantic, Central Indian, East Indian, West Pacific and East Pacific regions. We found sea surface temperature and sea surface height to be the most important predictors of current habitat for these penguins; physical features that are changing rapidly in the Southern Ocean. Our results indicated that the less severe RCP4.5 would lead to less habitat loss than the more severe RCP8.5. The five taxa of penguin may experience a general poleward redistribution of their preferred habitat, but with contrasting effects in the (i) change in total area of preferred habitat under climate change (ii) according to geographic region and (iii) the species (macaroni/royal vs. rockhopper populations). Our results provide further understanding on the regional impacts and vulnerability of species to climate change. 相似文献
70.
Madeleine Tissot Nanaë Gendre Andrew Hawken Klemens F. Strtkuhl Reinhard F. Stocker 《Developmental neurobiology》1997,32(3):281-297
We have studied the fate of olfactory afferents during metamorphic transformation of Drosophila melanogaster. Intracellular labeling of afferents from larval head chemosensilla suggests that the larval antennal lobe may be an olfactory target, whereas tritocerebral and suboesophageal centers are likely targets of gustatory sensilla. Application of monoclonal antibody 22C10 shows that the larval antennal nerve is the precursor of the adult antennal nerve and is used as a centripetal pathway for the adult afferents. Likely guidance cues are larval olfactory afferents that persist during early metamorphosis. P[GAL4] enhancer trap lines are introduced as efficient markers to follow the establishment of adult sensory projections. β-Galactosidase and the bovine TAU protein were used as reporter proteins, and their expression patterns are compared. P[GAL4] lines MT14 and KL116 demonstrate that adult antennal afferents have arrived in the antennal lobe 24 h after pupariation and extend to the contralateral lobe 6 h later. Line MT14 expresses GAL4 mostly in basiconic sensilla and in certain trichoid sensilla, whereas KL116 is specific for trichoid and a small subset of basiconic sensilla. In the antennal lobe, largely complementary subsets of glomeruli are labeled by the two lines, in agreement with the observation that particular types of sensilla project to particular target glomeruli. © 1997 John Wiley & Sons, Inc. J Neurobiol 32: 281–297, 1997. 相似文献