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Silvia Novohradská, Iuliia Ferling, Falk Hillmann
Infections with filamentous fungi are common to all animals, but attention is rising especially due to the increasing incidence and high mortality rates observed in immunocompromised human individuals. Here, Aspergillus fumigatus and other members of its genus are the leading causative agents. Attributes like their saprophytic life-style in various ecological niches coupled with nutritional flexibility and a broad host range have fostered the hypothesis that environmental predators could have been the actual target for some of their virulence determinants...
2017: Frontiers in Cellular and Infection Microbiology
Atsushi Tamada, Michihiro Igarashi
Left-right asymmetry is a fundamental feature of body plans, but its formation mechanisms and roles in functional lateralization remain unclear. Accumulating evidence suggests that left-right asymmetry originates in the cellular chirality. However, cell chirality has not yet been quantitatively investigated, mainly due to the absence of appropriate methods. Here we combine 3D Riesz transform-differential interference contrast (RT-DIC) microscopy and computational kinematic analysis to characterize chiral cellular morphology and motility...
December 19, 2017: Nature Communications
Xianzhong Xu, Alexander Eletsky, M Osman Sheikh, James H Prestegard, Christopher M West
Cullin-Ring-Ligases mediate protein polyubiquitination, a signal for degradation in the 26S-proteasome. The CRL1 class consists of Skp1/cullin-1/F-box protein/Rbx1 (SCF) complexes that cyclically associate with ubiquitin-E2 to build the polyubiquitin chain. Within the SCF complex, the 162-amino acid DdSkp1 from Dictyostelium bridges cullin-1 with an F-box protein (FBP), the specificity factor for substrate selection. The hydroxylation-dependent glycosylation of Pro143 of DdSkp1 by a pentasaccharide forms the basis of a novel O2-sensing mechanism in the social amoeba Dictyostelium and other protists...
December 18, 2017: Biochemistry
Andrea Nicolussi, Joe Dan Dunn, Georg Mlynek, Marzia Bellei, Marcel Zámocký, Gianantonio Battistuzzi, Kristina Djinovic-Carugo, Paul G Furtmüller, Thierry Soldati, Christian Obinger
Oxidation of halides and thiocyanate by heme peroxidases to antimicrobial oxidants is an important cornerstone in the innate immune system of mammals. Interestingly, phylogenetic and physiological studies suggest that homologous peroxidases are already present in mycetozoan eukaryotes such as Dictyostelium discoideum This social amoeba kills bacteria via phagocytosis for nutrient acquisition at its single-cell stage and for antibacterial defense at its multicellular stages. Here we demonstrate that peroxidase A from D...
December 14, 2017: Journal of Biological Chemistry
Andrew J Davidson, Clelia Amato, Peter A Thomason, Robert H Insall
Actin pseudopods induced by SCAR/WAVE drive normal migration and chemotaxis in eukaryotic cells. Cells can also migrate using blebs, in which the edge is driven forward by hydrostatic pressure instead of actin. In Dictyostelium discoideum, loss of SCAR is compensated by WASP moving to the leading edge to generate morphologically normal pseudopods. Here we use an inducible double knockout to show that cells lacking both SCAR and WASP are unable to grow, make pseudopods or, unexpectedly, migrate using blebs. Remarkably, amounts and dynamics of actin polymerization are normal...
November 30, 2017: Journal of Cell Biology
Yulia Artemenko, Peter N Devreotes
Chemotaxis, or migration up a gradient of a chemoattractant, is the best understood mode of directed migration. Studies using social amoeba Dictyostelium discoideum revealed that a complex signal transduction network of parallel pathways amplifies the response to chemoattractants, and leads to biased actin polymerization and protrusion of a pseudopod in the direction of a gradient. In contrast, molecular mechanisms driving other types of directed migration, for example, due to exposure to shear flow or electric fields, are not known...
November 9, 2017: Journal of Visualized Experiments: JoVE
William S Swatson, Mariko Katoh-Kurasawa, Gad Shaulsky, Stephen Alexander
Botanicals are widely used as dietary supplements and for the prevention and treatment of disease. Despite a long history of use, there is generally little evidence supporting the efficacy and safety of these preparations. Curcumin has been used to treat a myriad of human diseases and is widely advertised and marketed for its ability to improve health, but there is no clear understanding how curcumin interacts with cells and affects cell physiology. D. discoideum is a simple eukaryotic lead system that allows both tractable genetic and biochemical studies...
2017: PloS One
Robert J Huber, Sabateeshan Mathavarajah
Ceroid lipofuscinosis neuronal 5 (CLN5) is a member of a family of proteins that are linked to neuronal ceroid lipofuscinosis (NCL). This devastating neurological disorder, known commonly as Batten disease, affects all ages and ethnicities and is currently incurable. The precise function of CLN5, like many of the NCL proteins, remains to be elucidated. In this study, we report the localization, molecular function, and interactome of Cln5, the CLN5 homolog in the social amoeba Dictyostelium discoideum. Residues that are glycosylated in human CLN5 are conserved in the Dictyostelium homolog as are residues that are mutated in patients with CLN5 disease...
November 8, 2017: Cellular Signalling
Andrea Amaroli, Lorenzo Gallus, Sara Ferrando
The use of pyrethroids has increased throughout the world over the past few decades, as organophosphate, carbamate and organochlorine insecticides are being phased out. Permethrin is widely used in the USA for crops treatment, at concentrations around 750 × 10(3) μg/L. In our study 3.6 μg/L permethrin decreases the fission-rate and the fruiting bodies formation of slime mould Dictyostelium discoideum. Whereas 3.6 × 10(4) μg/L kills the 100% of amoebae, showing a 24 h-LC50 = 96.6 μg/L. This concentration induces an increase in the pseudocholinesterase activity as well as in both butyrylcholinesterase and heat-shock-protein 70 presence...
October 26, 2017: Chemosphere
Manuel Hotz, W James Nelson
Chemotaxis is a specialized form of directed cell migration important for normal development, wound healing, and cancer metastasis. In the social amoeba Dictyostelium discoideum, four signaling pathways act synergistically to maintain directional cell migration. However, it is unknown how these pathways are coordinated in space and time to achieve persistent chemotaxis. Here, we show that the mRNAs and proteins of these four chemotaxis pathways and actin are preferentially enriched at the cell front during dynamic cell migration, which requires the Pumilio-related RNA-binding protein Puf118...
November 8, 2017: Nature Communications
Xuehua Xu, Xi Wen, Douwe M Veltman, Ineke Keizer-Gunnink, Henderikus Pots, Arjan Kortholt, Tian Jin
Eukaryotic cells chemotax in a wide range of chemoattractant concentration gradients, and thus need inhibitory processes that terminate cell responses to reach adaptation while maintaining sensitivity to higher-concentration stimuli. However, the molecular mechanisms underlying inhibitory processes are still poorly understood. Here, we reveal a locally controlled inhibitory process in a GPCR-mediated signaling network for chemotaxis in Dictyostelium discoideum We identified a negative regulator of Ras signaling, C2GAP1, which localizes at the leading edge of chemotaxing cells and is activated by and essential for GPCR-mediated Ras signaling...
November 6, 2017: Proceedings of the National Academy of Sciences of the United States of America
Alix M Denoncourt, Alicia F Durocher, Valérie E Paquet, Steve J Charette
The amoeba Dictyostelium discoideum produces and secretes multilamellar bodies (MLBs) mainly composed of amoebal membranes upon digestion of bacteria. After their secretion, the fate of these MLBs remains unknown. The aim of this study was to determine if protozoa can internalize and digest secreted D. discoideum MLBs. Our results showed that MLBs were ingested by naive axenic D. discoideum cells (i. e. cells not exposed to bacteria and consequently not producing MLBs). Only a small fraction of the ingested MLBs were found in cells' post-lysosomes compared to undigestible beads suggesting that naive amoebae digest them...
October 14, 2017: European Journal of Cell Biology
Brittany M Neumann, Devin Kenney, Qi Wen, Arne Gericke
This work describes a method that utilizes a microfluidic gradient generator to develop lateral lipid gradients in supported lipid bilayers (SLB). This methodology that we have developed provides freedom of choice with respect to the lipid composition as well as the shape of the lipid gradient. For instance, the steepness of the gradient, within certain limits of its functional behavior, can be chosen based upon the experimental objectives. In addition, the device has the ability to create a protein or bivalent cation gradient in the aqueous phase above the lipid bilayer and to elicit a gradient specific response in the SLB...
November 1, 2017: Chemistry and Physics of Lipids
Katsunori Takahashi, Haruhisa Kikuchi, Van Hai Nguyen, Yoshiteru Oshima, Hirotaka Ishigaki, Junko Nakajima-Shimada, Yuzuru Kubohara
Differentiation-inducing factor-3 (DIF-3; 1-(3-chloro-2,6-dihydroxy-4-methoxyphenyl)hexan-1-one), which is found in the cellular slime mold Dictyostelium discoideum, is a potential candidate compound for the development of new medicines; DIF-3 and its derivatives possess several beneficial biological activities, including anti-tumor, anti-Trypanosoma cruzi, and immunoregulatory effects. To assess the relationship between the biological activities of DIF-3 and its chemical structure, particularly in regard to its alkoxy group and the length of the alkyl chains at the acyl group, we synthesized two derivatives of DIF-3, 1-(3-chloro-2,6-dihydroxy-4-methoxyphenyl)octan-1-one (DIF-3(+3)) and 1-(3-chloro-2,6-dihydroxy-4-butoxyphenyl)-hexan-1-one (Hex-DIF-3), and investigated their biological activities in vitro...
2017: Biological & Pharmaceutical Bulletin
Estefania Vidal-Henriquez, Vladimir Zykov, Eberhard Bodenschatz, Azam Gholami
In a reaction-diffusion-advection system, with a convectively unstable regime, a perturbation creates a wave train that is advected downstream and eventually leaves the system. We show that the convective instability coexists with a local absolute instability when a fixed boundary condition upstream is imposed. This boundary induced instability acts as a continuous wave source, creating a local periodic excitation near the boundary, which initiates waves travelling both up and downstream. To confirm this, we performed analytical analysis and numerical simulations of a modified Martiel-Goldbeter reaction-diffusion model with the addition of an advection term...
October 2017: Chaos
Albert Goldbeter
Sustained oscillations abound in biological systems. They occur at all levels of biological organization over a wide range of periods, from a fraction of a second to years, and with a variety of underlying mechanisms. They control major physiological functions, and their dysfunction is associated with a variety of physiological disorders. The goal of this review is (i) to give an overview of the main rhythms observed at the cellular and supracellular levels, (ii) to briefly describe how the study of biological rhythms unfolded in the course of time, in parallel with studies on chemical oscillations, (iii) to present the major roles of biological rhythms in the control of physiological functions, and (iv) the pathologies associated with the alteration, disappearance, or spurious occurrence of biological rhythms...
October 2017: Chaos
Zahra Eidi, Farshid Mohammad-Rafiee, Mohammad Khorrami, Azam Gholami
Chemotaxis is a ubiquitous biological phenomenon in which cells detect a spatial gradient of chemoattractant, and then move towards the source. Here we present a position-dependent advection-diffusion model that quantitatively describes the statistical features of the chemotactic motion of the social amoeba Dictyostelium discoideum in a linear gradient of cAMP (cyclic adenosine monophosphate). We fit the model to experimental trajectories that are recorded in a microfluidic setup with stationary cAMP gradients and extract the diffusion and drift coefficients in the gradient direction...
November 15, 2017: Soft Matter
Marek Malicki, Maro Iliopoulou, Christian Hammann
Transposable elements, identified in all eukaryotes, are mobile genetic units that can change their genomic position. Transposons usually employ an excision and reintegration mechanism, by which they change position, but not copy number. In contrast, retrotransposons amplify via RNA intermediates, increasing their genomic copy number. Hence, they represent a particular threat to the structural and informational integrity of the invaded genome. The social amoeba Dictyostelium discoideum, model organism of the evolutionary Amoebozoa supergroup, features a haploid, gene-dense genome that offers limited space for damage-free transposition...
2017: Frontiers in Microbiology
Barbara Pergolizzi, Salvatore Bozzaro, Enrico Bracco
Signal transduction through G-protein-coupled receptors (GPCRs) is central for the regulation of virtually all cellular functions, and it has been widely implicated in human diseases. These receptors activate a common molecular switch that is represented by the heterotrimeric G-protein generating a number of second messengers (cAMP, cGMP, DAG, IP3, Ca(2+) etc.), leading to a plethora of diverse cellular responses. Spatiotemporal regulation of signals generated by a given GPCR is crucial for proper signalling and is accomplished by a series of biochemical modifications...
October 19, 2017: International Journal of Molecular Sciences
Shigenori Hirose, Gong Chen, Adam Kuspa, Gad Shaulsky
Allorecognition is a key factor in Dictyostelium development and sociality. It is mediated by two polymorphic transmembrane proteins, TgrB1 and TgrC1, that contain extracellular immunoglobulin domains. TgrB1 and TgrC1 are necessary and sufficient for allorecognition and they carry out separate albeit overlapping functions in development, but their mechanism of action is unknown. Here we show that TgrB1 acts as a receptor and TgrC1 as its ligand in cooperative aggregation and differentiation. The proteins bind each other in a sequence-specific manner, TgrB1 exhibits a cell-autonomous function, and TgrC1 acts non-cell-autonomously...
October 16, 2017: Journal of Cell Science
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