scholarly journals A TOR (target of rapamycin) and nutritional phosphoproteome of fission yeast reveals novel targets in networks conserved in humans

Open Biology ◽  
2021 ◽  
Vol 11 (4) ◽  
Author(s):  
Lenka Halova ◽  
David Cobley ◽  
Mirita Franz-Wachtel ◽  
Tingting Wang ◽  
Kaitlin R. Morrison ◽  
...  
Keyword(s):  
Fission Yeast ◽  
Nitrogen Stress ◽  
Cell Integrity ◽  
Cdc2 Kinase ◽  
Control Of Gene Expression ◽  
Mitotic Control ◽  
Indirect Consequence ◽  
Novel Targets ◽  
A Site ◽  
Induced Changes

Fluctuations in TOR, AMPK and MAP-kinase signalling maintain cellular homeostasis and coordinate growth and division with environmental context. We have applied quantitative, SILAC mass spectrometry to map TOR and nutrient-controlled signalling in the fission yeast Schizosaccharomyces pombe . Phosphorylation levels at more than 1000 sites were altered following nitrogen stress or Torin1 inhibition of the TORC1 and TORC2 networks that comprise TOR signalling. One hundred and thirty of these sites were regulated by both perturbations, and the majority of these (119) new targets have not previously been linked to either nutritional or TOR control in either yeasts or humans. Elimination of AMPK inhibition of TORC1, by removal of AMPK α ( ssp2::ura4 + ), identified phosphosites where nitrogen stress-induced changes were independent of TOR control. Using a yeast strain with an ATP analogue-sensitized Cdc2 kinase, we excluded sites that were changed as an indirect consequence of mitotic control modulation by nitrogen stress or TOR signalling. Nutritional control of gene expression was reflected in multiple targets in RNA metabolism, while significant modulation of actin cytoskeletal components points to adaptations in morphogenesis and cell integrity networks. Reduced phosphorylation of the MAPKK Byr1, at a site whose human equivalent controls docking between MEK and ERK, prevented sexual differentiation when resources were sparse but not eliminated.

scholarly journals Slm9, a Novel Nuclear Protein Involved in Mitotic Control in Fission Yeast

Genetics ◽  
2000 ◽  
Vol 155 (2) ◽  
pp. 623-631
Author(s):  
Junko Kanoh ◽  
Paul Russell
Keyword(s):  
Cell Cycle ◽  
Fission Yeast ◽  
Cell Elongation ◽  
Nuclear Protein ◽  
G1 Arrest ◽  
Permissive Temperature ◽  
Cdc2 Kinase ◽  
Synthetic Lethal ◽  
Cycle Arrest ◽  
Novel Protein

Abstract In the fission yeast Schizosaccharomyces pombe, as in other eukaryotic cells, Cdc2/cyclin B complex is the key regulator of mitosis. Perhaps the most important regulation of Cdc2 is the inhibitory phosphorylation of tyrosine-15 that is catalyzed by Wee1 and Mik1. Cdc25 and Pyp3 phosphatases dephosphorylate tyrosine-15 and activate Cdc2. To isolate novel activators of Cdc2 kinase, we screened synthetic lethal mutants in a cdc25-22 background at the permissive temperature (25°). One of the genes, slm9, encodes a novel protein of 807 amino acids. Slm9 is most similar to Hir2, the histone gene regulator in budding yeast. Slm9 protein level is constant and Slm9 is localized to the nucleus throughout the cell cycle. The slm9 disruptant is delayed at the G2-M transition as indicated by cell elongation and analysis of DNA content. Inactivation of Wee1 fully suppressed the cell elongation phenotype caused by the slm9 mutation. The slm9 mutant is defective in recovery from G1 arrest after nitrogen starvation. The slm9 mutant is also UV sensitive, showing a defect in recovery from the cell cycle arrest after UV irradiation.

scholarly journals Specific Functional Features of the Cell Integrity MAP Kinase Pathway in the Dimorphic Fission Yeast Schizosaccharomyces japonicus

2021 ◽  
Vol 7 (6) ◽  
pp. 482
Author(s):  
Elisa Gómez-Gil ◽  
Alejandro Franco ◽  
Beatriz Vázquez-Marín ◽  
Francisco Prieto-Ruiz ◽  
Armando Pérez-Díaz ◽  
...  
Keyword(s):  
Fission Yeast ◽  
Environmental Changes ◽  
Yeast Species ◽  
Mapk Signaling ◽  
Fine Tuning ◽  
Mitogen Activated Protein Kinase ◽  
Major Influence ◽  
Cell Integrity ◽  
Mitogen Activated Protein ◽  
Functional Features

Mitogen activated protein kinase (MAPK) signaling pathways execute essential functions in eukaryotic organisms by transducing extracellular stimuli into adaptive cellular responses. In the fission yeast model Schizosaccharomyces pombe the cell integrity pathway (CIP) and its core effector, MAPK Pmk1, play a key role during regulation of cell integrity, cytokinesis, and ionic homeostasis. Schizosaccharomyces japonicus, another fission yeast species, shows remarkable differences with respect to S. pombe, including a robust yeast to hyphae dimorphism in response to environmental changes. We show that the CIP MAPK module architecture and its upstream regulators, PKC orthologs Pck1 and Pck2, are conserved in both fission yeast species. However, some of S. pombe’s CIP-related functions, such as cytokinetic control and response to glucose availability, are regulated differently in S. japonicus. Moreover, Pck1 and Pck2 antagonistically regulate S. japonicus hyphal differentiation through fine-tuning of Pmk1 activity. Chimeric MAPK-swapping experiments revealed that S. japonicus Pmk1 is fully functional in S. pombe, whereas S. pombe Pmk1 shows a limited ability to execute CIP functions and promote S. japonicus mycelial development. Our findings also suggest that a modified N-lobe domain secondary structure within S. japonicus Pmk1 has a major influence on the CIP signaling features of this evolutionarily diverged fission yeast.

Effect of Diamagnetic A2+ Substitution on the Magnetic and Ferroelectric Properties of the Bi1−xAxFeO3 Multiferroics

2007 ◽  
Vol 1034 ◽  
Author(s):  
V. A. Khomchenko ◽  
D. A. Kiselev ◽  
J. M. Vieira ◽  
Li Jian ◽  
A. M. L. Lopes ◽  
...  
Keyword(s):  
Spin Structure ◽  
Ionic Radius ◽  
Ferroelectric Properties ◽  
Piezoresponse Force Microscopy ◽  
Weak Ferromagnetism ◽  
Force Microscopy ◽  
Microscopy Data ◽  
A Site ◽  
Induced Changes ◽  
Spiral Spin

AbstractInvestigation of crystal structure, magnetic and local ferroelectric properties of the diamagnetically-doped Bi1−xAxFeO3 (A= Ca, Sr, Pb, Ba; x= 0.2, 0.3) ceramic samples has been carried out. It has been shown that the solid solutions have a rhombohedrally distorted perovskite structure described by the space group R3c. Piezoresponse force microscopy data have revealed the existence of the spontaneous ferroelectric polarization in the samples at room temperature. Magnetization measurements have shown that the magnetic state of these compounds is determined by the ionic radius of the substituting elements. A-site substitution with the biggest ionic radius ions has been found to suppress the spiral spin structure of BiFeO3 and to result in the appearance of weak ferromagnetism. The magnetic properties have been discussed in terms of doping- induced changes in the magnetic anisotropy.

scholarly journals Negative Functional Interaction Between Cell Integrity MAPK Pathway and Rho1 GTPase in Fission Yeast

Genetics ◽  
2013 ◽  
Vol 195 (2) ◽  
pp. 421-432 ◽  
Author(s):  
Raul A. Viana ◽  
Mario Pinar ◽  
Teresa Soto ◽  
Pedro M. Coll ◽  
Jose Cansado ◽  
...  
Keyword(s):  
Fission Yeast ◽  
Mapk Pathway ◽  
Cell Integrity ◽  
Functional Interaction

Site-specific mutagenesis of cdc2+, a cell cycle control gene of the fission yeast Schizosaccharomyces pombe

1986 ◽  
Vol 6 (10) ◽  
pp. 3523-3530
Author(s):  
R Booher ◽  
D Beach
Keyword(s):  
Schizosaccharomyces Pombe ◽  
Fission Yeast ◽  
Cell Cycle Control ◽  
Temperature Sensitive ◽  
Protein Kinase Activity ◽  
Atp Binding Site ◽  
Leu2 Gene ◽  
Cdc2 Gene ◽  
A Site

The cdc2+ gene of Schizosaccharomyces pombe is homologous to the CDC28 gene of Saccharomyces cerevisiae. Both genes share limited homology with vertebrate protein kinases and have protein kinase activity. cdc2+ has been subjected to mutagenesis in vitro. A null allele of the gene, constructed by insertion of the S. cerevisiae LEU2 gene into a site within the gene, has a phenotype similar to that of many temperature-sensitive alleles of cdc2. Mutations within the predicted ATP-binding site and in a region which may be a site of phosphorylation result in loss of cdc2+ activity. A single substitution of Gly-146 to Asp-146 has been identified in cdc2-1w, a dominant activated allele of the gene. The four introns within the cdc2+ gene have been deleted. The resulting gene not only functions in fission yeast but also rescues cdc28(Ts) strains of S. cerevisiae, a property which is not shared by the genomic cdc2+ gene.

scholarly journals Characterization of erythrocyte quality during the refrigerated storage of whole blood containing di-(2-ethylhexyl) phthalate

Blood ◽  
1984 ◽  
Vol 64 (6) ◽  
pp. 1270-1276 ◽  
Author(s):  
TN Estep ◽  
RA Pedersen ◽  
TJ Miller ◽  
KR Stupar
Keyword(s):  
Blood Cell ◽  
Red Blood Cell ◽  
Whole Blood ◽  
Refrigerated Storage ◽  
Cell Integrity ◽  
Normal Morphology ◽  
Plasma Hemoglobin ◽  
Induced Changes ◽  
Ethylhexyl Phthalate

Abstract Di-(2-ethylhexyl) phthalate (DEHP) accumulates in blood brought into contact with materials utilizing this compound as a plasticizer. To determine whether this phthalate diester affects red blood cell integrity, we have compared cell morphology, plasma hemoglobin accumulation, micro-vesicle production, and the concentration of intracellular metabolites and electrolytes of erythrocytes from blood stored at 4 degrees C with and without DEHP. When sufficient emulsified DEHP was mixed with blood to give a final concentration of 300 micrograms/mL, plasma hemoglobin accumulation was reduced by an average of 70%, the percentage of cells exhibiting normal morphology was enhanced by at least 20-fold, and the volume of microvesicles released from red blood cells was reduced by 50% after 35 days of refrigerated storage compared to the values obtained from corresponding samples stored without added phthalate. Similar effects were observed regardless of whether blood was stored in nonplasticized polypropylene or tri-(2-ethylhexyl) trimellitate plasticized polyvinylchloride containers and with DEHP solubilized by a variety of emulsifiers. When 300 micrograms/mL DEHP was added to stored blood containing erythrocytes predominantly in the echinocyte conformation, many of the cells reverted to the normal discoid morphology. The addition of this quantity of DEHP to blood had no significant effect on the course of storage-induced changes in erythrocyte adenosine triphosphate (ATP), 2,3-diphosphoglycerate (2,3-DPG), sodium or potassium concentrations. The data are consistent with the hypothesis that DEHP inhibits the deterioration of the red blood cell membrane that results from the refrigerated storage of whole blood.

scholarly journals Influence of Diets with Varying Essential/Nonessential Amino Acid Ratios on Mouse Lifespan

Nutrients ◽  
2019 ◽  
Vol 11 (6) ◽  
pp. 1367 ◽  
Author(s):  
Claudia Romano ◽  
Giovanni Corsetti ◽  
Vincenzo Flati ◽  
Evasio Pasini ◽  
Anna Picca ◽  
...  
Keyword(s):  
Caloric Intake ◽  
Essential Amino Acids ◽  
Whole Body ◽  
Control Group ◽  
Cell Integrity ◽  
Structural Modifications ◽  
Food And Water Intake ◽  
Whole Body Metabolism ◽  
Standard Laboratory Diet ◽  
Induced Changes

An adequate intake of essential (EAA) and non-essential amino acids (NEAA) is crucial to preserve cell integrity and whole-body metabolism. EAA introduced with diet may be insufficient to meet the organismal needs, especially under increased physiological requirements or in pathological conditions, and may condition lifespan. We therefore examined the effects of iso-caloric and providing the same nitrogenous content diets, any diet containing different stoichiometric blends of EAA/NEAA, on mouse lifespan. Three groups of just-weaned male Balb/C mice were fed exclusively with special diets with varying EAA/NEAA ratios, ranging from 100%/0% to 0%/100%. Three additional groups of mice were fed with different diets, two based on casein as alimentary proteins, one providing the said protein, one reproducing the amino acidic composition of casein, and the third one, the control group, was fed by a standard laboratory diet. Mouse lifespan was inversely correlated with the percentage of NEAA introduced with each diet. Either limiting EAA, or exceeding NEAA, induced rapid and permanent structural modifications on muscle and adipose tissue, independently of caloric intake. These changes significantly affected food and water intake, body weight, and lifespan. Dietary intake of varying EAA/NEAA ratios induced changes in several organs and profoundly influenced murine lifespan. The balanced content of EAA provided by dietary proteins should be considered as the preferable means for “optimal” nutrition and the elevated or unbalanced intake of NEAA provided by food proteins may negatively affect the health and lifespan of mice.

Baroreflex modulation of heart rate and initiation of atrial activation in dogs

1988 ◽  
Vol 255 (3) ◽  
pp. H503-H513 ◽  
Author(s):  
R. B. Schuessler ◽  
T. E. Canavan ◽  
J. P. Boineau ◽  
J. L. Cox
Keyword(s):  
Blood Pressure ◽  
Heart Rate ◽  
Right Atrial ◽  
Autonomic Blockade ◽  
Left And Right ◽  
Atrial Activation ◽  
The Right ◽  
A Site ◽  
Induced Changes ◽  
Cardiac Nerves

In open-chest dogs, blood pressure was regulated by titrating doses of phenylephrine and nitroprusside to determine its effect on heart rate and pacemaker location. Changes in blood pressure correlated with changes in heart rate (r = 0.86). Activation time mapping demonstrated multicentric atrial activation, with a site of origin-rate relationship. The fastest pacemakers were located in the most cranial regions and slowest in the most caudal areas. In this chloralose-morphine anesthetized model, autonomic blockade with atropine and propranolol suggests that acute baroreflex-induced changes in heart rate were mediated exclusively by either increased sympathetic or parasympathetic tone and were not associated with inhibition of the opposite system. Division of right and left thoracic cardiac nerves indicated the left sympathetics participated in the baroreflex in 50% of the animals and the left parasympathetics in 90% of the animals. Both the right sympathetics and parasympathetics were active in the baroreflex in all animals. The data demonstrate that physiological heart rate response is regulated through an extensive system of right atrial pacemakers modulated by both left and right efferent cardiac nerves.

On the Role of Calpain and Rho Proteins in Regulating Integrin-induced Signaling

1999 ◽  
Vol 82 (08) ◽  
pp. 385-391 ◽  
Author(s):  
Joan Fox
Keyword(s):  
Signaling Molecules ◽  
Cytoskeletal Proteins ◽  
Adherent Cells ◽  
Rho Proteins ◽  
Ligand Interactions ◽  
Platelet Aggregate ◽  
And Migration ◽  
Key Steps ◽  
A Site ◽  
Induced Changes

SummaryThe integrin family of transmembrane receptors plays an essential role in inducing the adhesion of cells to the extracellular matrix. In some cases, members of this family of receptors can bind soluble ligands or can bind receptors on other cells and, in this way, mediate interactions between cells. In all cases, once an integrin has bound, ligand signals are transmitted across the occupied integrin. These signals culminate in changes in the behavior of the cell appropriate for the adherent state of the cell. For example, in the case of platelets, an end result of the signaling induced by binding of fibrinogen to αIIbβ3 in a platelet aggregate is a reorganization of the cytoskeleton that leads to retraction of externally-bound fibrin by clots.1,2 In the case of neutrophils, cytoskeletal changes following the integrininduced interaction of neutrophils with endothelial cells lead to the migration of neutrophils into a site of injury.3,4 Other examples of the consequences of integrin-induced signaling in adherent cells include the trafficking of lymphocytes and migration of cells during development, angiogenesis, and metastasis.5-7 Numerous signaling molecules have been shown to be activated following integrin-ligand interactions.8 Many of these associate in complexes with ligand-occupied integrin and cytoskeletal proteins. However, in general, little is known about the key steps involved regarding integrin-induced changes in the behavior of adherent cells. The present chapter reviews steps involved in integrin-induced signaling, describes the evidence that calpain is one of the signaling molecules involved in this signal transduction, and discusses potential mechanisms by which cleavage of cytoskeletal proteins and signaling molecules by calpain may regulate the integrin-induced changes in cell behavior.

scholarly journals Gene and Protein Expression Pilot Profiling and Biomarkers in an Experimental Mouse Model of Hypertensive Glaucoma

2009 ◽  
Vol 234 (8) ◽  
pp. 918-930 ◽  
Author(s):  
Molly M. Walsh ◽  
Haiqing Yi ◽  
Julie Friedman ◽  
Kyoung-in Cho ◽  
Nomingerel Tserentsoodol ◽  
...  
Keyword(s):  
Protein Expression ◽  
Serum Amyloid ◽  
Cell Integrity ◽  
Molecular Processes ◽  
Experimental Glaucoma ◽  
Molecular Events ◽  
Gene And Protein Expression ◽  
Inflammatory Processes ◽  
Ganglion Neurons ◽  
Induced Changes

Glaucoma is a group of genetically heterogeneous neurodegenerative disorders causing the degeneration of the ganglion neurons of the retina. Increased intraocular pressure (IOP) is a hallmark risk factor promoting the death of ganglion neurons of the retina in glaucoma. Yet, the molecular processes underlying the degeneration of these neurons by increased IOP are not understood. To gain insight into the early molecular events and discover biomarkers induced by IOP, we performed gene and protein expression profiling to compare retinas of eyes with and without high IOP in a rodent model of experimental glaucoma. This pilot study found that the IOP-mediated changes in the transcription levels of a restricted set of genes implicated in peroxisomal and mitochondrial function, modulation of neuron survival and inflammatory processes, were also accompanied by changes in the levels of proteins encoded by the same genes. With the exception of the inflammatory markers, serum amyloid-A1 (SAA1) and serum amyloid-A2 (SAA2), the IOP-induced changes in protein expression were restricted to ganglion neurons of the retina and they were detected also in the vitreous, thus suggesting an early IOP-mediated loss of ganglion cell integrity. Interestingly, SAA1 and SAA2 were induced in retinal microglia cells, whereas they were reduced in sera of IOP-responsive mice. Hence, this study defines novel IOP-induced molecular processes, biomarkers and sources thereof, and it further validates the extension of the analyses herein reported to other genes modulated by IOP.

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