Research, Research Articles

A humanized yeast-based toolkit for monitoring phosphatidylinositol 3-kinase activity at both single cell and population levels

Julia María Coronas-Serna1, Teresa Fernández-Acero1, María Molina1 and Víctor J. Cid1

In this study, a humanized yeast system for functional studies on higher eukaryotic Phosphatidylinositol 3-kinase (PI3K) was developed by restricting PI3K activity in yeast to specific plasma membrane microdomains, utilizing engineered reporters to monitor activity at a single-cell level and employing novel tools to study the performance of yeast plasma membrane (PM) microdomain-directed PI3K, revealing location-specific effects on yeast growth and endocytosis.

A chemical genetic screen reveals a role for proteostasis in capsule and biofilm formation by Cryptococcus neoformans

François L. Mayer1, Eddy Sánchez-León1, James W. Kronstad1

This study demonstrates that the bipolar disorder drug lithium inhibits the formation of key virulence factors, biofilm, and polysaccharide capsule, in Cryptococcus neoformans by dysregulating the ubiquitin/proteasome system, shedding light on the impact of lithium and providing insights into potential alternative pharmaceutical approaches for combating this fungal pathogen.

Nutritional and meiotic induction of transiently heritable stress resistant states in budding yeast

Heldder Gutierrez1, Bakhtiyar Taghizada1, and Marc D. Meneghini1

This study demonstrates that transient exposures to environmental stresses induce persistent states of elevated stress resistance in yeast cells, termed cellular memory, suggesting a form of epigenetic inheritance, and shows that this phenomenon occurs not only in meiotically produced spores but also in haploid cells subjected to glucose withdrawal, adding new insights into the developmentally and nutritionally induced cellular memory.

Specific mutations in the permease domain of septal protein SepJ differentially affect functions related to multicellularity in the filamentous cyanobacterium Anabaena

Félix Ramos-León1, Sergio Arévalo1, Vicente Mariscal1 and Enrique Flores1

In this study, the multifunctional roles of the SepJ protein in the multicellular function of the Anabaena filament were investigated, revealing that specific amino acids and stretches within the protein are essential for the formation of long filaments, heterocyst differentiation, and intercellular communication, shedding light on the structure and diverse functions of SepJ in the model heterocyst-forming cyanobacterium Anabaena sp. strain PCC 7120.

Trehalose-6-phosphate promotes fermentation and glucose repression in Saccharomyces cerevisiae

Rebeca L. Vicente1,2, Lucie Spina1, Jose P.L. Gómez1, Sebastien Dejean3, Jean-Luc Parrou1 and Jean Marie François1,4

This study examined the capability of trehalose-6-phosphate synthase (TPS1) homologues from various species to complement the phenotypic defects of a Saccharomyces cerevisiae tps1 mutant, resulting in the classification of complementation into different groups based on metabolic patterns and fermentation capacity, shedding light on the role of TPS1 and trehalose-6-phosphate (T6P) as critical factors in sugar fermentation and glucose repression.

The translationally controlled tumor protein TCTP is involved in cell cycle progression and heat stress response in the bloodstream form of Trypanosoma brucei

Borka Jojic1, Simona Amodeo1,2 and Torsten Ochsenreiter1

This study reveals the involvement of the translationally controlled tumor protein TCTP in cell cycle regulation and heat stress response in the bloodstream form of Trypanosoma brucei, shedding light on its role in these cellular processes.

Single telomere length analysis in Ustilago maydis, a high-resolution tool for examining fungal telomere length distribution and C-strand 5’-end processing

Ganduri Swapna1, Eun Young Yu1 and Neal F. Lue1, 2

This article introduces the development of single telomere length analysis (STELA) for Ustilago maydis, a basidiomycete fungus, enabling the precise measurement of telomere lengths and distributions. The study demonstrates STELA's utility in revealing the existence of relatively short telomeres in wild-type cells, preferential loss of long telomeres in a mutant defective in telomere replication, and the characterization of telomere C-strand 5’ ends, highlighting U. maydis as a strong model for telomere research.

Temporal analysis of the autophagic and apoptotic phenotypes in Leishmania parasites

Louise Basmaciyan1, Laurence Berry2, Julie Gros3, Nadine Azas3 and Magali Casanova3

This article details a comprehensive analysis of miltefosine-induced cell death and autophagy in Leishmania major, providing criteria for clear identification of apoptotic and autophagic cells, demonstrating the sequential nature of autophagy followed by apoptosis in nutrient-deprived conditions, and cautioning against using the generic kinase inhibitor staurosporine as a Leishmania apoptosis inducer, with the aim of improving the understanding of these processes and their targeting for new anti-leishmanial drugs.

Snf1 cooperates with the CWI MAPK pathway to mediate the degradation of Med13 following oxidative stress

Stephen D. Willis1, David C. Stieg1, Kai Li Ong2, Ravina Shah1,3, Alexandra K. Strich1,4, Julianne H. Grose2 and Katrina F. Cooper1

This article explores the response of eukaryotic cells to environmental stress, highlighting the role of the conserved cyclin C-Cdk8 kinase in determining pro-survival or pro-death programs. Specifically, it discusses how oxidative stress triggers the destruction of Med13 by the SCFGrr1 ubiquitin ligase, releasing cyclin C to promote mitochondrial fission and cell death in Saccharomyces cerevisiae. Additionally, it reveals that the AMP kinase Snf1 activates a separate degron in Med13, contributing to the complex regulation of Med13 degradation following H2O2 stress through the coordination of the cell wall integrity and MAPK pathways.

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A cobalt concentration sensitive Btu-like system facilitates cobalamin uptake in Anabaena sp. PCC 7120

February 20, 2024

Metal homeostasis is central to all forms of life, as metals are essential micronutrients with toxic effects at elevated levels. Our results provide novel information on the uptake of cobalamin and the regulation of the cellular cobalt content in cyanobacteria.

Predictable regulation of survival by intratumoral microbe-immune crosstalk in patients with lung adenocarcinoma

February 19, 2024

Intratumoral microbiota can regulate the tumor immune microenvironment (TIME) and mediate tumor prognosis by promoting inflammatory response or inhibiting anti-tumor effects. Our study demonstrated that intratumoral microbiota-immune crosstalk was strongly associated with prognosis in LUAD patients, which would provide new targets for the development of precise therapeutic strategies.

Two TonB-dependent outer membrane transporters involved in heme uptake in Anabaena sp. PCC 7120

January 9, 2024

Low availability of micronutrients such as iron has enforced the evolution of uptake systems in all kingdoms of life. In our study, we conclude that heme transport might not be restricted to Anabaena, but at the same time is not specific to a cyanobacterial order and thus might be related to the habitat of origin, a notion which needs to be challenged in the future.

The last two transmembrane helices in the APC-type FurE transporter act as an intramolecular chaperone essential for concentrative ER-exit

January 5, 2024

FurE is a H+ symporter specific for the cellular uptake of uric acid, allantoin, uracil, and toxic nucleobase analogues in the fungus Aspergillus nidulans. Being member of the NCS1 protein family, FurE is structurally related to the APC-superfamily of transporters.

Extracellular DNA secreted in yeast cultures is metabolism-specific and inhibits cell proliferation

November 23, 2023

Our study demonstrates that extracellular DNA released by living cells can impact the growth rate of Saccharomyces cerevisiae cultures, showing similarities to extrachromosomal circular DNA and leading to cell cycle arrest in the S phase, suggesting potential new functional roles of exDNA.

Basal level of ppGpp coordinates Escherichia coli cell heterogeneity and ampicillin resistance and persistence

October 25, 2023

The universal stringent response alarmone ppGpp (guanosine penta and tetra phosphates) plays a crucial role in various aspects of fundamental cell physiology (e.g., cell growth rate, cell size) and thus bacterial tolerance to and survival of external stresses, including antibiotics. In tihs study, we discuss the fundamental role of basal level of ppGpp in regulating cell homogeneity and ampicillin persistence.

Investigation of the acetic acid stress response in Saccharomyces cerevisiae with mutated H3 residues

August 18, 2023

Yeast cells respond to acetic acid in diverse ways. Here, we have elucidated the deleterious effects of acetic acid on different histone mutants

The coenzyme B12 precursor 5,6-dimethylbenzimidazole is a flavin antagonist in Salmonella

August 17, 2023

Here we investigated why 5,6-dimethylbenzimidazole (DMB) inhibits in S. Typhimurium. Briefly, we determined that the structural similarities of the substituted benzene ring of DMB with the isoalloxazine moiety of flavins is responsible for the deleterious effects of this CoB12 precursor.

Yeast gene KTI13 (alias DPH8) operates in the initiation step of diphthamide synthesis on elongation factor 2

August 8, 2023

We show here that apart from its effector role for Elongator-dependent tRNA modification in yeast, Kti13 alias Dph8 also operates in step one of the diphthamide modification pathway.

Caspase 3 exhibits a yeast metacaspase proteostasis function that protects mitochondria from toxic TDP43 aggregates

July 10, 2023

Caspase 3 activation is a hallmark of cell death and there is a strong correlation between elevated protease activity and evolving pathology in neurodegenerative disease, such as amyotrophic lateral sclerosis (ALS). These results suggest that caspase 3 is not inherently pathogenic, but may act as a compensatory proteostasis factor, to limit TDP-43 protein inclusions and protect organelle function in aggregation related degenerative disease.

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