Understanding the biological significance of diphosphoinositol polyphosphates (‘inositol pyrophosphates’)

2007 ◽  
Vol 74 ◽  
pp. 211-221 ◽  
Author(s):  
Stephen B. Shears
Keyword(s):  
Cell Signalling ◽  
Biological Significance ◽  
Inositol Polyphosphates ◽  
Future Studies ◽  
Inositol Pyrophosphates ◽  
The Many ◽  
Derivatives Of

Among the many derivatives of the inositol-based signalling family are a subgroup that possess diphosphates. In this review, some recent research into the actions of these specialized polyphosphates is analysed, and key goals for future studies are identified, which, it is hoped, will result in the wider cell-signalling community giving considerably greater attention to this intriguing but relatively neglected class of inositol polyphosphates.

scholarly journals Novel Substrates for Kinases Involved in the Biosynthesis of Inositol Pyrophosphates and Their Enhancement of ATPase Activity of a Kinase

Molecules ◽  
2021 ◽  
Vol 26 (12) ◽  
pp. 3601
Author(s):  
Raja Mohanrao ◽  
Ruth Manorama ◽  
Shubhra Ganguli ◽  
Mithun C. Madhusudhanan ◽  
Rashna Bhandari ◽  
...  
Keyword(s):  
Enzyme Activity ◽  
Atpase Activity ◽  
Catalytic Domain ◽  
Inositol Phosphate ◽  
Substrate Recognition ◽  
Competitive Inhibitor ◽  
Inositol Polyphosphates ◽  
Inositol Pyrophosphate ◽  
Phosphate Donor ◽  
Inositol Pyrophosphates

IP6K and PPIP5K are two kinases involved in the synthesis of inositol pyrophosphates. Synthetic analogs or mimics are necessary to understand the substrate specificity of these enzymes and to find molecules that can alter inositol pyrophosphate synthesis. In this context, we synthesized four scyllo-inositol polyphosphates—scyllo-IP5, scyllo-IP6, scyllo-IP7 and Bz-scyllo-IP5—from myo-inositol and studied their activity as substrates for mouse IP6K1 and the catalytic domain of VIP1, the budding yeast variant of PPIP5K. We incubated these scyllo-inositol polyphosphates with these kinases and ATP as the phosphate donor. We tracked enzyme activity by measuring the amount of radiolabeled scyllo-inositol pyrophosphate product formed and the amount of ATP consumed. All scyllo-inositol polyphosphates are substrates for both the kinases but they are weaker than the corresponding myo-inositol phosphate. Our study reveals the importance of axial-hydroxyl/phosphate for IP6K1 substrate recognition. We found that all these derivatives enhance the ATPase activity of VIP1. We found very weak ligand-induced ATPase activity for IP6K1. Benzoyl-scyllo-IP5 was the most potent ligand to induce IP6K1 ATPase activity despite being a weak substrate. This compound could have potential as a competitive inhibitor.

scholarly journals Roundup®, but Not Roundup-Ready® Corn, Increases Mortality of Drosophila melanogaster

Toxics ◽  
2019 ◽  
Vol 7 (3) ◽  
pp. 38
Author(s):  
Becky Talyn ◽  
Rachael Lemon ◽  
Maryam Badoella ◽  
Darwin Melchiorre ◽  
Maryori Villalobos ◽  
...  
Keyword(s):  
Drosophila Melanogaster ◽  
Genetically Modified ◽  
Genetically Modified Foods ◽  
Herbicide Application ◽  
Reproductive Behaviors ◽  
Future Studies ◽  
Toxicological Effects ◽  
The Us ◽  
Biochemical Mechanisms ◽  
The Many

Genetically modified foods have become pervasive in diets of people living in the US. By far the most common genetically modified foods either tolerate herbicide application (HT) or produce endogenous insecticide (Bt). To determine whether these toxicological effects result from genetic modification per se, or from the increase in herbicide or insecticide residues present on the food, we exposed fruit flies, Drosophila melanogaster, to food containing HT corn that had been sprayed with the glyphosate-based herbicide Roundup®, HT corn that had not been sprayed with Roundup®, or Roundup® in a variety of known glyphosate concentrations and formulations. While neither lifespan nor reproductive behaviors were affected by HT corn, addition of Roundup® increased mortality with an LC50 of 7.1 g/L for males and 11.4 g/L for females after 2 days of exposure. Given the many genetic tools available, Drosophila are an excellent model system for future studies about genetic and biochemical mechanisms of glyphosate toxicity.

scholarly journals Inositol polyphosphates intersect with signaling and metabolic networks via two distinct mechanisms

2016 ◽  
Vol 113 (44) ◽  
pp. E6757-E6765 ◽  
Author(s):  
Mingxuan Wu ◽  
Lucy S. Chong ◽  
David H. Perlman ◽  
Adam C. Resnick ◽  
Dorothea Fiedler
Keyword(s):  
Ribosome Biogenesis ◽  
Metabolic Networks ◽  
Central Line ◽  
Eukaryotic Cell ◽  
Nucleotide Metabolism ◽  
Telomere Maintenance ◽  
Inositol Polyphosphates ◽  
Protein Targets ◽  
Messenger Molecules ◽  
Inositol Pyrophosphates

Inositol-based signaling molecules are central eukaryotic messengers and include the highly phosphorylated, diffusible inositol polyphosphates (InsPs) and inositol pyrophosphates (PP-InsPs). Despite the essential cellular regulatory functions of InsPs and PP-InsPs (including telomere maintenance, phosphate sensing, cell migration, and insulin secretion), the majority of their protein targets remain unknown. Here, the development of InsP and PP-InsP affinity reagents is described to comprehensively annotate the interactome of these messenger molecules. By using the reagents as bait, >150 putative protein targets were discovered from a eukaryotic cell lysate (Saccharomyces cerevisiae). Gene Ontology analysis of the binding partners revealed a significant overrepresentation of proteins involved in nucleotide metabolism, glucose metabolism, ribosome biogenesis, and phosphorylation-based signal transduction pathways. Notably, we isolated and characterized additional substrates of protein pyrophosphorylation, a unique posttranslational modification mediated by the PP-InsPs. Our findings not only demonstrate that the PP-InsPs provide a central line of communication between signaling and metabolic networks, but also highlight the unusual ability of these molecules to access two distinct modes of action.

The Problem of Detecting Changes in the Incidence of Schizophrenia

1993 ◽  
Vol 162 (2) ◽  
pp. 212-218 ◽  
Author(s):  
R. E. Kendell ◽  
D. E. Malcolm ◽  
W. Adams
Keyword(s):  
Diagnostic Criteria ◽  
Future Studies ◽  
Western Countries ◽  
Admission Rates ◽  
Methodological Problems ◽  
The Many ◽  
The Uk ◽  
The Relationship ◽  
First Admission

Despite reports of falling first-admission rates for schizophrenia in the UK and other Western countries, it would be rash to conclude that the incidence of schizophrenia is falling. An attempt was made to tackle the many methodological problems and sources of bias influencing the relationship between admission rates and incidence in an analysis of inception rates for schizophrenia and other psychoses in Edinburgh between 1971 and 1989. However it was calculated, the inception rate for schizophrenia fell significantly, but because there was evidence that diagnostic criteria for schizophrenia had narrowed between 1971 and 1989, and because a substantial and changing proportion of recorded first admissions were not true first admissions, it was impossible to conclude that the incidence of schizophrenia had fallen. Changes in the incidence of psychiatric syndromes are difficult to establish, particularly in retrospect, and future studies must pay more attention to the many possible confounding influences.

An overview of the biological significance of endogenous gases: new roles for old molecules

2007 ◽  
Vol 35 (5) ◽  
pp. 1138-1141 ◽  
Author(s):  
L. Li ◽  
P.K. Moore
Keyword(s):  
Cell Function ◽  
Cell Signalling ◽  
Control Cell ◽  
Biological Significance ◽  
Molecular Targets ◽  
The Body ◽  
Biologically Active ◽  
Central Nervous System Function ◽  
Signalling Molecules ◽  
Nervous System Function

Biologically active gases that occur naturally in the body include nitric oxide (NO), carbon monoxide (CO) and hydrogen sulfide (H2S). Each of these molecules is synthesized by enzymes which have been characterized biochemically and pharmacologically, and each acts, via well-established molecular targets, to effect physiological and/or pathophysiological functions within the body. Major biological roles that appear to be common to all three gases include the regulation of vascular homoeostasis and central nervous system function. It is becoming increasingly clear that both the synthesis and the biological activity of each gas are, to some extent, regulated by the presence of the others, and as such it is necessary to consider these molecules not in isolation but acting together to control cell function. Additional, more speculative candidates for gaseous cell signalling molecules include ammonia, acetaldehyde, sulfur dioxide and nitrous oxide. Whether such molecules also play a role in regulating body function remains to be determined.

Cell surface heparan sulfates mediate internalization of the PWWP/HATH domain of HDGF via macropinocytosis to fine-tune cell signalling processes involved in fibroblast cell migration

2010 ◽  
Vol 433 (1) ◽  
pp. 127-138 ◽  
Author(s):  
Chia-Hui Wang ◽  
Fabian Davamani ◽  
Shih-Che Sue ◽  
Shao-Chen Lee ◽  
Po-long Wu ◽  
...  
Keyword(s):  
Cell Migration ◽  
Cell Surface ◽  
Receptor Binding ◽  
Cell Signalling ◽  
Biological Significance ◽  
Matrix Metalloproteases ◽  
Membrane Receptor ◽  
Mutant Form ◽  
Heparin Binding ◽  
Nih 3T3

HDGF (hepatoma-derived growth factor) stimulates cell proliferation by functioning on both sides of the plasma membrane as a ligand for membrane receptor binding to trigger cell signalling and as a stimulator for DNA synthesis in the nucleus. Although HDGF was initially identified as a secretory heparin-binding protein, the biological significance of its heparin-binding ability remains to be determined. In the present study we demonstrate that cells devoid of surface HS (heparan sulfate) were unable to internalize HDGF, HATH (N-terminal domain of HDGF consisting of amino acid residues 1–100, including the PWWP motif) and HATH(K96A) (single-site mutant form of HATH devoid of receptor binding activity), suggesting that the binding of HATH to surface HS is important for HDGF internalization. We further demonstrate that both HATH and HATH(K96A) could be internalized through macropinocytosis after binding to the cell surface HS. Interestingly, HS-mediated HATH(K96A) internalization is found to exhibit an inhibitory effect on cell migration and proliferation in contrast with that observed for HATH action on NIH 3T3 cells, suggesting that HDGF exploits the innate properties of both cell surface HS and membrane receptor via the HATH domain to affect related cell signalling processes. The present study indicates that MAPK (mitogen-activated protein kinase) signalling pathways could be affected by the HS-mediated HATH internalization to regulate cell migration in NIH 3T3 fibroblasts, as judged from the differential effect of HATH and HATH(K96A) treatment on the expression level of matrix metalloproteases.

scholarly journals Holins in Bacteria, Eukaryotes, and Archaea: Multifunctional Xenologues with Potential Biotechnological and Biomedical Applications

2014 ◽  
Vol 197 (1) ◽  
pp. 7-17 ◽  
Author(s):  
Milton H. Saier ◽  
Bhaskara L. Reddy
Keyword(s):  
Cell Death ◽  
Biomedical Applications ◽  
Cell Lysis ◽  
Gram Negative Bacteria ◽  
Bacterial Genomes ◽  
Future Studies ◽  
Virion Release ◽  
Cytoplasmic Membranes ◽  
Domains Of Life ◽  
The Many

Holins form pores in the cytoplasmic membranes of bacteria for the primary purpose of releasing endolysins that hydrolyze the cell wall and induce cell death. Holins are encoded within bacteriophage genomes, where they promote cell lysis for virion release, and within bacterial genomes, where they serve a diversity of potential or established functions. These include (i) release of gene transfer agents, (ii) facilitation of programs of differentiation such as those that allow sporulation and spore germination, (iii) contribution to biofilm formation, (iv) promotion of responses to stress conditions, and (v) release of toxins and other proteins. There are currently 58 recognized families of holins and putative holins with members exhibiting between 1 and 4 transmembrane α-helical spanners, but many more families have yet to be discovered. Programmed cell death in animals involves holin-like proteins such as Bax and Bak that may have evolved from bacterial holins. Holin homologues have also been identified in archaea, suggesting that these proteins are ubiquitous throughout the three domains of life. Phage-mediated cell lysis of dual-membrane Gram-negative bacteria also depends on outer membrane-disrupting “spanins” that function independently of, but in conjunction with, holins and endolysins. In this minireview, we provide an overview of their modes of action and the first comprehensive summary of the many currently recognized and postulated functions and uses of these cell lysis systems. It is anticipated that future studies will result in the elucidation of many more such functions and the development of additional applications.

scholarly journals Ploidy dynamics in aphid host cells harboring bacterial symbionts

2021 ◽  
Author(s):  
Tomonari Nozaki ◽  
Shuji Shigenobu
Keyword(s):  
Acyrthosiphon Pisum ◽  
Biological Significance ◽  
Large Cell ◽  
Host Cells ◽  
Bacterial Symbionts ◽  
Buchnera Aphidicola ◽  
Ploidy Levels ◽  
Future Studies ◽  
Functional Roles ◽  
Aphid Host

AbstractAphids have evolved bacteriocytes or symbiotic host cells that harbor the obligate mutualistic bacterium Buchnera aphidicola. Because of the large cell size (approximately 100 μm in diameter) of bacteriocytes and their pivotal role in nutritional symbiosis, researchers have considered that these cells are highly polyploid and assumed that bacteriocyte polyploidy may be essential for the symbiotic relationship between the aphid and the bacterium. However, little is known about the ploidy levels and dynamics of aphid bacteriocytes. Here, we quantitatively analyzed the ploidy levels in the bacteriocytes of the pea-aphid Acyrthosiphon pisum. Image-based fluorometry revealed the hyper polyploidy of the bacteriocytes ranging from 16- to 256-ploidy throughout the lifecycle. Bacteriocytes of adult parthenogenetic viviparous females were mainly 64-128C DNA levels, while those of sexual morphs (oviparous females and males) were consisted of 64C, and 32-64C cells, respectively. During post-embryonic development of viviparous females, the ploidy level of bacteriocytes increased substantially, from 16-32C at birth to 128-256C in actively reproducing adults. These results suggest that the ploidy levels are dynamically regulated among phenotypes and during development. Our comprehensive and quantitative data provides a foundation for future studies to understand the functional roles and biological significance of the polyploidy of insect bacteriocytes.

scholarly journals Metabolomic Variability of Different Genotypes of Cashew by LC-Ms and Correlation with Near-Infrared Spectroscopy as a Tool for Fast Phenotyping

Metabolites ◽  
2019 ◽  
Vol 9 (6) ◽  
pp. 121 ◽  
Author(s):  
Alves Filho ◽  
Silva ◽  
Lima ◽  
Ribeiro ◽  
Silva ◽  
...  
Keyword(s):  
Near Infrared ◽  
High Resolution Mass Spectrometry ◽  
Low Cost ◽  
Ultra Performance Liquid Chromatography ◽  
Future Studies ◽  
Chemical Profiling ◽  
Cashew Apple ◽  
Hydroxybutanoic Acid ◽  
Non Destructive ◽  
Derivatives Of

The objective of the present work was to develop an advanced fast phenotyping tool to explore the cashew apple compositions from different genotypes, based on a portable near-infrared (MicroNIR) spectroscopy. This will be in addition to associating the variability of the respective cashew apple pulps with the genotypes by ultra-performance liquid chromatography (UPLC), coupled with high-resolution mass spectrometry (HRMS). The NIR analysis is a non-destructive, low-cost procedure that provides prompt results, while considering the morphology of different cashew apples (shape, size, and color). The UPLC-HRMS analysis is characterized by specific bioactive compounds, such as the derivatives of hydroxybutanoic acid, galloyl, and flavonoids. Furthermore, both techniques allowed the identification of a group of accessions, which presented similarities among the chemical profiling. However, to improve the understanding of cashew chemical and physical variability, further variables related to the cashew apple composition, such as edaphoclimatic conditions, should be considered for future studies. These approaches lead to the conclusion that these two tools are useful for the maintenance of BAG-Caju (Cashew Germplasm Bank) and for the cashew-breeding program.

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