scholarly journals Nitric Oxide and Electrophilic Cyclopentenone Prostaglandins in Redox signaling, Regulation of Cytoskeleton Dynamics and Intercellular Communication

2021 ◽  
Vol 9 ◽  
Author(s):  
Ángel Bago ◽  
Miguel A. Íñiguez ◽  
Juan M. Serrador
Keyword(s):  
Nitric Oxide ◽  
Intercellular Communication ◽  
Cellular Response ◽  
Current Knowledge ◽  
Actin Dynamics ◽  
Actin Binding ◽  
Post Translational Modification ◽  
Cytoskeleton Organization ◽  
Cyclopentenone Prostaglandins ◽  
Electrophilic Lipids

Nitric oxide (NO) and electrophilic cyclopentenone prostaglandins (CyPG) are local mediators that modulate cellular response to oxidative stress in different pathophysiological processes. In particular, there is increasing evidence about their functional role during inflammation and immune responses. Although the mechanistic details about their relationship and functional interactions are still far from resolved, NO and CyPG share the ability to promote redox-based post-translational modification (PTM) of proteins that play key roles in cellular homeostasis, signal transduction and transcription. NO-induced S-nitrosylation and S-glutathionylation as well as cyclopentenone-mediated adduct formation, are a few of the main PTMs by which intra- and inter-cellular signaling are regulated. There is a growing body of evidence indicating that actin and actin-binding proteins are susceptible to covalent PTM by these agents. It is well known that the actin cytoskeleton is key for the establishment of interactions among leukocytes, endothelial and muscle cells, enabling cellular activation and migration. In this review we analyze the current knowledge about the actions exerted by NO and CyPG electrophilic lipids on the regulation of actin dynamics and cytoskeleton organization, and discuss some open questions regarding their functional relevance in the regulation of intercellular communication.

scholarly journals In Vivo Importance of Actin Nucleotide Exchange Catalyzed by Profilin

2000 ◽  
Vol 150 (4) ◽  
pp. 895-904 ◽  
Author(s):  
Amy K. Wolven ◽  
Lisa D. Belmont ◽  
Nicole M. Mahoney ◽  
Steven C. Almo ◽  
David G. Drubin
Keyword(s):  
Point Mutations ◽  
Fluid Phase ◽  
Intrinsic Rate ◽  
Actin Dynamics ◽  
Actin Binding ◽  
Nucleotide Exchange ◽  
Actin Organization ◽  
Cytoskeleton Organization

The actin monomer-binding protein, profilin, influences the dynamics of actin filaments in vitro by suppressing nucleation, enhancing nucleotide exchange on actin, and promoting barbed-end assembly. Profilin may also link signaling pathways to actin cytoskeleton organization by binding to the phosphoinositide PIP2 and to polyproline stretches on several proteins. Although activities of profilin have been studied extensively in vitro, the significance of each of these activities in vivo needs to be tested. To study profilin function, we extensively mutagenized the Saccharomyces cerevisiae profilin gene (PFY1) and examined the consequences of specific point mutations on growth and actin organization. The actin-binding region of profilin was shown to be critical in vivo. act1-157, an actin mutant with an increased intrinsic rate of nucleotide exchange, suppressed defects in actin organization, cell growth, and fluid-phase endocytosis of pfy1-4, a profilin mutant defective in actin binding. In reactions containing actin, profilin, and cofilin, profilin was required for fast rates of actin filament turnover. However, Act1-157p circumvented the requirement for profilin. Based on the results of these studies, we conclude that in living cells profilin promotes rapid actin dynamics by regenerating ATP actin from ADP actin–cofilin generated during filament disassembly.

Exploiting S-nitrosylation for cancer therapy: facts and perspectives

2020 ◽  
Vol 477 (19) ◽  
pp. 3649-3672
Author(s):  
Salvatore Rizza ◽  
Giuseppe Filomeni
Keyword(s):  
Nitric Oxide ◽  
Cancer Biology ◽  
Synthetic Lethality ◽  
Current Knowledge ◽  
Tissue Homeostasis ◽  
Loss Of Function ◽  
Post Translational Modification ◽  
Cellular Processes ◽  
Insight Into

S-nitrosylation, the post-translational modification of cysteines by nitric oxide, has been implicated in several cellular processes and tissue homeostasis. As a result, alterations in the mechanisms controlling the levels of S-nitrosylated proteins have been found in pathological states. In the last few years, a role in cancer has been proposed, supported by the evidence that various oncoproteins undergo gain- or loss-of-function modifications upon S-nitrosylation. Here, we aim at providing insight into the current knowledge about the role of S-nitrosylation in different aspects of cancer biology and report the main anticancer strategies based on: (i) reducing S-nitrosylation-mediated oncogenic effects, (ii) boosting S-nitrosylation to stimulate cell death, (iii) exploiting S-nitrosylation through synthetic lethality.

scholarly journals Capturing Salmonella SspH2 Host Targets in Virus-Like Particles

2021 ◽  
Vol 8 ◽  
Author(s):  
Margaux De Meyer ◽  
Igor Fijalkowski ◽  
Veronique Jonckheere ◽  
Delphine De Sutter ◽  
Sven Eyckerman ◽  
...  
Keyword(s):  
Protein Complexes ◽  
Host Protein ◽  
Actin Dynamics ◽  
Actin Binding ◽  
Secretion Systems ◽  
Immune Signaling ◽  
Cytoskeleton Organization ◽  
Host Cytoplasm ◽  
Serovar Typhimurium ◽  
Type Iii Protein Secretion

In the context of host-pathogen interactions, gram-negative bacterial virulence factors, such as effectors, may be transferred from bacterial to eukaryotic host cytoplasm by multicomponent Type III protein secretion systems (T3SSs). Central to Salmonella enterica serovar Typhimurium (S. Typhimurium) pathogenesis is the secretion of over 40 effectors by two T3SSs encoded within pathogenicity islands SPI-1 and SPI-2. These effectors manipulate miscellaneous host cellular processes, such as cytoskeleton organization and immune signaling pathways, thereby permitting host colonization and bacterial dissemination. Recent research on effector biology provided mechanistic insights for some effectors. However, for many effectors, clearly defined roles and host target repertoires—further clarifying effector interconnectivity and virulence networks—are yet to be uncovered. Here we demonstrate the utility of the recently described viral-like particle trapping technology Virotrap as an effective approach to catalog S. Typhimurium effector-host protein complexes (EH-PCs). Mass spectrometry-based Virotrap analysis of the novel E3 ubiquitin ligase SspH2 previously shown to be implicated in modulating actin dynamics and immune signaling, exposed known host interactors PFN1 and−2 besides several putative novel, interconnected host targets. Network analysis revealed an actin (-binding) cluster among the significantly enriched hits for SspH2, consistent with the known localization of the S-palmitoylated effector with actin cytoskeleton components in the host. We show that Virotrap complements the current state-of-the-art toolkit to study protein complexes and represents a valuable means to screen for effector host targets in a high-throughput manner, thereby bridging the knowledge gap between effector-host interplay and pathogenesis.

scholarly journals Actin force generation in vesicle formation: mechanistic insights from cryo-electron tomography

2021 ◽  
Author(s):  
Daniel Serwas ◽  
Matthew Akamatsu ◽  
Amir Moayed ◽  
Karthik Vegesna ◽  
Ritvik Vasan ◽  
...  
Keyword(s):  
Actin Filament ◽  
Structural Information ◽  
Electron Tomography ◽  
Neck Region ◽  
Force Generation ◽  
Actin Dynamics ◽  
Actin Binding ◽  
Cytoskeleton Organization ◽  
Cryo Electron Tomography ◽  
Dynamics Simulations

Actin filament assembly provides force during clathrin-mediated endocytosis. Here, cryo-electron tomography analysis of actin filament number, organization, and orientation during clathrin-mediated endocytosis in intact human cells revealed that force generation is robust despite variance in network organization. Actin dynamics simulations incorporating a measured branch angle of 68 +/- 9° indicate that sufficient force to drive endocytosis can be generated through polymerization, and that assembly is triggered from 4 +/- 2 founding "mother" filaments, consistent with the tomography data. The actin-binding protein Hip1R decorates the entire endocytic invagination, including the neck region. Simulations showed that the unexpected Hip1R neck localization targets filament growth to this region, improving internalization efficiency and robustness. Actin cytoskeleton organization described here allowed direct translation of structural information to mechanism.

scholarly journals Nitric oxide and plant mineral nutrition: current knowledge

2019 ◽  
Vol 70 (17) ◽  
pp. 4461-4476 ◽  
Author(s):  
Agustina Buet ◽  
Andrea Galatro ◽  
Facundo Ramos-Artuso ◽  
Marcela Simontacchi
Keyword(s):  
Nitric Oxide ◽  
Current Knowledge ◽  
Plant Morphology ◽  
Plant Performance ◽  
Post Translational Modification ◽  
Exciting Field ◽  
Nutrient Imbalances ◽  
Multiple Processes ◽  
Iron And Zinc ◽  
Nutrient Homeostasis

Abstract Plants under conditions of essential mineral deficiency trigger signaling mechanisms that involve common components. Among these components, nitric oxide (NO) has been identified as a key participant in responses to changes in nutrient availability. Usually, nutrient imbalances affect the levels of NO in specific plant tissues, via modification of its rate of synthesis or degradation. Changes in the level of NO affect plant morphology and/or trigger responses associated with nutrient homeostasis, mediated by its interaction with reactive oxygen species, phytohormones, and through post-translational modification of proteins. NO-related events constitute an exciting field of research to understand how plants adapt and respond to conditions of nutrient shortage. This review summarizes the current knowledge on NO as a component of the multiple processes related to plant performance under conditions of deficiency in mineral nutrients, focusing on macronutrients such as nitrogen, phosphate, potassium, and magnesium, as well as micronutrients such as iron and zinc.

scholarly journals N-terminal modification of actin by acetylation and arginylation determines the architecture and assembly rate of linear and branched actin networks

2020 ◽  
Author(s):  
Samantha M. Chin ◽  
Tomoyuki Hatano ◽  
Lavanya Sivashanmugam ◽  
Andrejus Suchenko ◽  
Anna S. Kashina ◽  
...  
Keyword(s):  
Cell Migration ◽  
Binding Proteins ◽  
Molecular Mechanisms ◽  
Leading Edge ◽  
Actin Dynamics ◽  
Actin Binding ◽  
Actin Network ◽  
Post Translational Modification ◽  
Actin Binding Proteins ◽  
N Terminus

AbstractThe great diversity in actin network architectures and dynamics is exploited by cells to drive fundamental biological processes, including cell migration, endocytosis and cell division. While it is known that this versatility is the result of the many actin-remodeling activities of actin-binding proteins, recent work implicates post-translational modification of the actin N-terminus by either acetylation or arginylation itself as an equally important regulatory mechanism. However, the molecular mechanisms by which acetylation and arginylation alter the properties of actin are not well understood. Here, we directly compare how processing, and modification of the N-terminus of actin affects its intrinsic polymerization dynamics and its remodeling by actin-binding proteins that are essential for cell migration. We find that in comparison to acetylated actin, arginylated actin reduces intrinsic as well as formin-mediated elongation and Arp2/3-mediated nucleation. By contrast, there are no significant differences in Cofilin-mediated severing. Taken together, these results suggest that cells can employ the differently modified actins to precisely regulate actin dynamics. In addition, unprocessed, or non-acetylated actin show very different effects on formin-mediated-elongation, Arp2/3-mediated nucleation, and severing by Cofilin. Altogether, this study shows that the nature of the N-terminus of actin can induce distinct actin network dynamics, which can be differentially used by cells to locally finetune actin dynamics at distinct cellular locations, such as at the leading edge.

scholarly journals Malonyl-proteome profiles of Staphylococcus aureus reveal lysine malonylation modification in enzymes involved in energy metabolism

2021 ◽  
Vol 19 (1) ◽  
Author(s):  
Yanan Shi ◽  
Jingjing Zhu ◽  
Yan Xu ◽  
Xiaozhao Tang ◽  
Zushun Yang ◽  
...  
Keyword(s):  
Staphylococcus Aureus ◽  
Energy Metabolism ◽  
Active Sites ◽  
Current Knowledge ◽  
Tricarboxylic Acid Cycle ◽  
Protein A ◽  
Pentose Phosphate ◽  
Post Translational Modification ◽  
Bacterial Physiology ◽  
Dihydrolipoyl Dehydrogenase

Abstract Background Protein lysine malonylation, a novel post-translational modification (PTM), has been recently linked with energy metabolism in bacteria. Staphylococcus aureus is the third most important foodborne pathogen worldwide. Nonetheless, substrates and biological roles of malonylation are still poorly understood in this pathogen. Results Using anti-malonyl-lysine antibody enrichment and high-resolution LC-MS/MS analysis, 440 lysine-malonylated sites were identified in 281 proteins of S. aureus strain. The frequency of valine in position − 1 and alanine at + 2 and + 4 positions was high. KEGG pathway analysis showed that six categories were highly enriched, including ribosome, glycolysis/gluconeogenesis, pentose phosphate pathway (PPP), tricarboxylic acid cycle (TCA), valine, leucine, isoleucine degradation, and aminoacyl-tRNA biosynthesis. In total, 31 malonylated sites in S. aureus shared homology with lysine-malonylated sites previously identified in E. coli, indicating malonylated proteins are highly conserved among bacteria. Key rate-limiting enzymes in central carbon metabolic pathways were also found to be malonylated in S. aureus, namely pyruvate kinase (PYK), 6-phosphofructokinase, phosphoglycerate kinase, dihydrolipoyl dehydrogenase, and F1F0-ATP synthase. Notably, malonylation sites were found at or near protein active sites, including KH domain protein, thioredoxin, alanine dehydrogenase (ALD), dihydrolipoyl dehydrogenase (LpdA), pyruvate oxidase CidC, and catabolite control protein A (CcpA), thus suggesting that lysine malonylation may affect the activity of such enzymes. Conclusions Data presented herein expand the current knowledge on lysine malonylation in prokaryotes and indicate the potential roles of protein malonylation in bacterial physiology and metabolism.

Nitric oxide signalling in plant interactions with pathogenic fungi and oomycetes

2020 ◽  
Author(s):  
Tereza Jedelská ◽  
Lenka Luhová ◽  
Marek Petřivalský
Keyword(s):  
Nitric Oxide ◽  
Current Knowledge ◽  
Biotic Interactions ◽  
Decisive Role ◽  
Pathogenic Fungi ◽  
Plant Colonization ◽  
No Production ◽  
Plant Interactions ◽  
Oriented Growth ◽  
Plant Pathogen Interactions

Abstract Nitric oxide (NO) and reactive nitrogen species have emerged as crucial signalling and regulatory molecules across all organisms. In plants, fungi and fungi-like oomycetes, NO is involved in the regulation of multiple processes during their growth, development, reproduction, responses to the external environment and biotic interactions. It has become evident that NO is produced and used as signalling and defence cues by both partners in multiple forms of plant interactions with their microbial counterparts, ranging from symbiotic to pathogenic modes. This review summarizes current knowledge on NO role in plant-pathogen interactions, focused on biotrophic, necrotrophic and hemibiotrophic fungi and oomycetes. Actual advances and gaps in the identification of NO sources and fate in plant and pathogen cells are discussed. We review the decisive role of time- and site-specific NO production in germination, oriented growth and active penetration of filamentous pathogens to the host tissues, as well in pathogen recognition, and defence activation in plants. Distinct functions of NO are highlighted on diverse interactions of host plants with fungal and oomycete pathogens of different lifestyles, where NO in interplay with reactive oxygen species govern successful plant colonization, cell death and resistance establishment.

scholarly journals Villin Severing Activity Enhances Actin-based Motility In Vivo

2007 ◽  
Vol 18 (3) ◽  
pp. 827-838 ◽  
Author(s):  
Céline Revenu ◽  
Matthieu Courtois ◽  
Alphée Michelot ◽  
Cécile Sykes ◽  
Daniel Louvard ◽  
...  
Keyword(s):  
Shigella Flexneri ◽  
Actin Dynamics ◽  
Actin Binding ◽  
Loss Of Function ◽  
Mesenchymal Transition ◽  
Capping Protein ◽  
Function Strategy ◽  
In Cells

Villin, an actin-binding protein associated with the actin bundles that support microvilli, bundles, caps, nucleates, and severs actin in a calcium-dependant manner in vitro. We hypothesized that the severing activity of villin is responsible for its reported role in enhancing cell plasticity and motility. To test this hypothesis, we chose a loss of function strategy and introduced mutations in villin based on sequence comparison with CapG. By pyrene-actin assays, we demonstrate that this mutant has a strongly reduced severing activity, whereas nucleation and capping remain unaffected. The bundling activity and the morphogenic effects of villin in cells are also preserved in this mutant. We thus succeeded in dissociating the severing from the three other activities of villin. The contribution of villin severing to actin dynamics is analyzed in vivo through the actin-based movement of the intracellular bacteria Shigella flexneri in cells expressing villin and its severing variant. The severing mutations abolish the gain of velocity induced by villin. To further analyze this effect, we reconstituted an in vitro actin-based bead movement in which the usual capping protein is replaced by either the wild type or the severing mutant of villin. Confirming the in vivo results, villin-severing activity enhances the velocity of beads by more than two-fold and reduces the density of actin in the comets. We propose a model in which, by severing actin filaments and capping their barbed ends, villin increases the concentration of actin monomers available for polymerization, a mechanism that might be paralleled in vivo when an enterocyte undergoes an epithelio-mesenchymal transition.

scholarly journals PDZ and LIM Domain-Encoding Genes: Molecular Interactions and their Role in Development

2007 ◽  
Vol 7 ◽  
pp. 1470-1492 ◽  
Author(s):  
Aartjan J. W. te Velthuis ◽  
Christoph P. Bagowski
Keyword(s):  
Current Knowledge ◽  
Pdz Domain ◽  
Cell Lineage ◽  
Lim Domain ◽  
Specific Expression ◽  
Cytoskeleton Organization ◽  
Signaling Complex ◽  
Lim Domains ◽  
Gene Structures ◽  
Encoding Genes

PDZ/LIM genes encode a group of proteins that play very important, but diverse, biological roles. They have been implicated in numerous vital processes, e.g., cytoskeleton organization, neuronal signaling, cell lineage specification, organ development, and oncogenesis.In mammals, there are ten genes that encode for both a PDZ domain, and one or several LIM domains: four genes of the ALP subfamily (ALP, Elfin, Mystique, and RIL), three of the Enigma subfamily (Enigma, Enigma Homolog, and ZASP), the two LIM kinases (LIMK1 and LIMK2), and the LIM only protein 7 (LMO7). Functionally, all PDZ and LIM domain proteins share an important trait, i.e., they can associate with and/or influence the actin cytoskeleton.We review here the PDZ and LIM domain—encoding genes and their different gene structures, their binding partners, and their role in development and disease. Emphasis is laid on the important questions: why the combination of a PDZ domain with one or more LIM domains is found in such a diverse group of proteins, and what role the PDZ/LIM module could have in signaling complex assembly and localization.Furthermore, the current knowledge on splice form specific expression and the function of these alternative transcripts during vertebrate development will be discussed, since another source of complexity for the PDZ and LIM domain—encoding proteins is introduced by alternative splicing, which often creates different domain combinations.

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