scholarly journals Effects of Simulated Microgravity on the Proteome and Secretome of the Polyextremotolerant Black Fungus Knufia chersonesos

2021 ◽  
Vol 12 ◽  
Author(s):  
Donatella Tesei ◽  
Abby J. Chiang ◽  
Markus Kalkum ◽  
Jason E. Stajich ◽  
Ganesh Babu Malli Mohan ◽  
...  
Keyword(s):  
Ribosome Biogenesis ◽  
Molecular Mechanisms ◽  
Simulated Microgravity ◽  
Outer Space ◽  
Extreme Environments ◽  
Cellular Level ◽  
Cell Physiology ◽  
Morphological Alterations ◽  
Translational Machinery ◽  
Black Fungi

Black fungi are a group of melanotic microfungi characterized by remarkable polyextremotolerance. Due to a broad ecological plasticity and adaptations at the cellular level, it is predicted that they may survive in a variety of extreme environments, including harsh niches on Earth and Mars, and in outer space. However, the molecular mechanisms aiding survival, especially in space, are yet to be fully elucidated. Based on these premises, the rock-inhabiting black fungus Knufia chersonesos (Wt) and its non-melanized mutant (Mut) were exposed to simulated microgravity—one of the prevalent features characterizing space conditions—by growing the cultures in high-aspect-ratio vessels (HARVs). Qualitative and quantitative proteomic analyses were performed on the mycelia and supernatant of culture medium (secretome) to assess alterations in cell physiology in response to low-shear simulated microgravity (LSSMG) and to ultimately evaluate the role of cell-wall melanization in stress survival. Differential expression was observed for proteins involved in carbohydrate and lipid metabolic processes, transport, and ribosome biogenesis and translation via ribosomal translational machinery. However, no evidence of significant activation of stress components or starvation response was detected, except for the scytalone dehydratase, enzyme involved in the synthesis of dihydroxynaphthalene (DNH) melanin, which was found to be upregulated in the secretome of the wild type and downregulated in the mutant. Differences in protein modulation were observed between K. chersonesos Wt and Mut, with several proteins being downregulated under LSSMG in the Mut when compared to the Wt. Lastly, no major morphological alterations were observed following exposure to LSSMG. Similarly, the strains’ survivability was not negatively affected. This study is the first to characterize the response to simulated microgravity in black fungi, which might have implications on future astrobiological missions.

scholarly journals Nucleolar Organization and Functions in Health and Disease

Cells ◽  
2020 ◽  
Vol 9 (3) ◽  
pp. 526 ◽  
Author(s):  
Ursula Stochaj ◽  
Stephanie C. Weber
Keyword(s):  
Stress Responses ◽  
Ribosome Biogenesis ◽  
Molecular Mechanisms ◽  
Rrna Genes ◽  
Cell Physiology ◽  
Ribosomal Subunits ◽  
Diamond Blackfan Anemia ◽  
Health And Disease ◽  
Progeria Syndrome ◽  
Hutchinson Gilford Progeria Syndrome

The nucleolus is a prominent, membraneless compartment found within the nucleus of eukaryotic cells. It forms around ribosomal RNA (rRNA) genes, where it coordinates the transcription, processing, and packaging of rRNA to produce ribosomal subunits. Recent efforts to characterize the biophysical properties of the nucleolus have transformed our understanding of the assembly and organization of this dynamic compartment. Indeed, soluble macromolecules condense from the nucleoplasm to form nucleoli through a process called liquid–liquid phase separation. Individual nucleolar components rapidly exchange with the nucleoplasm and separate within the nucleolus itself to form distinct subcompartments. In addition to its essential role in ribosome biogenesis, the nucleolus regulates many aspects of cell physiology, including genome organization, stress responses, senescence and lifespan. Consequently, the nucleolus is implicated in several human diseases, such as Hutchinson–Gilford progeria syndrome, Diamond–Blackfan anemia, and various forms of cancer. This Special Issue highlights new insights into the physical and molecular mechanisms that control the architecture and diverse functions of the nucleolus, and how they break down in disease.

scholarly journals Interaction of light and gravity signals as a mechanism of counteracting alterations caused by simulated microgravity in proliferating plant cells

2020 ◽  
Author(s):  
Aránzazu Manzano ◽  
Veronica Pereda-Loth ◽  
Anne de Bures ◽  
Julio Sáez-Vásquez ◽  
Raúl Herranz ◽  
...  
Keyword(s):  
Plant Development ◽  
Ribosome Biogenesis ◽  
Simulated Microgravity ◽  
Life Support ◽  
Cellular Level ◽  
Differential Sensitivity ◽  
Molecular Alterations ◽  
Gravitational Stress ◽  
To Come ◽  
Spaceflight Experiments

Abstract Background Light and gravity are fundamental cues for plant development on Earth. In space, understanding the effects of changing conditions affecting to these two stimuli is key for optimizing the life support systems to come with space exploration. Simulated microgravity is useful as a complement to real spaceflight experiments into refining our knowledge of early plant development adaptation to extraterrestrial environments. Results In wild type Arabidopsis and in mutants of the two genes of the essential nucleolar protein nucleolin (nuc1 and nuc2), the use of an extended toolbox of cell proliferation, cell growth and ribosome biogenesis markers, has allowed us to show that the incorporation of an illumination regime, in this case photoperiod, has been sufficient to attenuate or suppress the effects caused by gravitational stress at the cellular level in the root meristem. These results are consistent with other experiments carried out at real and simulated microgravity in which early plant development is nominal when the environmental conditions are optimal (nutrients, light, temperature, humidity). Conclusions Light signals may total or partially replace gravity signals significantly improving plant growth and development in microgravity. Despite that, molecular alterations are still compatible with the expected adaptation mechanisms that should be better understood. The differential sensitivity of nuc1 and nuc2 mutants to gravitational stress points to new strategies to produce more resilient plants to travel with humans in new extraterrestrial endeavors.

Galectin-3: A factotum in carcinogenesis bestowing an archery for prevention

Tumor Biology ◽  
2021 ◽  
Vol 43 (1) ◽  
pp. 77-96
Author(s):  
T. Jeethy Ram ◽  
Asha Lekshmi ◽  
Thara Somanathan ◽  
K. Sujathan
Keyword(s):  
Cancer Progression ◽  
Molecular Mechanisms ◽  
Cancer Metastasis ◽  
Epithelial Mesenchymal Transition ◽  
Therapy Resistance ◽  
Cellular Level ◽  
Clinical Samples ◽  
Innovative Strategy ◽  
Mesenchymal Transition ◽  
Galectin 3

Cancer metastasis and therapy resistance are the foremost hurdles in oncology at the moment. This review aims to pinpoint the functional aspects of a unique multifaceted glycosylated molecule in both intracellular and extracellular compartments of a cell namely galectin-3 along with its metastatic potential in different types of cancer. All materials reviewed here were collected through the search engines PubMed, Scopus, and Google scholar. Among the 15 galectins identified, the chimeric gal-3 plays an indispensable role in the differentiation, transformation, and multi-step process of tumor metastasis. It has been implicated in the molecular mechanisms that allow the cancer cells to survive in the intravascular milieu and promote tumor cell extravasation, ultimately leading to metastasis. Gal-3 has also been found to have a pivotal role in immune surveillance and pro-angiogenesis and several studies have pointed out the importance of gal-3 in establishing a resistant phenotype, particularly through the epithelial-mesenchymal transition process. Additionally, some recent findings suggest the use of gal-3 inhibitors in overcoming therapeutic resistance. All these reports suggest that the deregulation of these specific lectins at the cellular level could inhibit cancer progression and metastasis. A more systematic study of glycosylation in clinical samples along with the development of selective gal-3 antagonists inhibiting the activity of these molecules at the cellular level offers an innovative strategy for primary cancer prevention.

scholarly journals Testing Lab-on-a-Chip Technology for Culturing Human Melanoma Cells under Simulated Microgravity

Cancers ◽  
2021 ◽  
Vol 13 (3) ◽  
pp. 402
Author(s):  
Dawid Przystupski ◽  
Agata Górska ◽  
Olga Michel ◽  
Agnieszka Podwin ◽  
Patrycja Śniadek ◽  
...  
Keyword(s):  
Simulated Microgravity ◽  
Lab On A Chip ◽  
Human Keratinocytes ◽  
Melanoma Cells ◽  
Short Exposure ◽  
Biological Research ◽  
Cell Physiology ◽  
Caspase Activity ◽  
Chip Technology ◽  
Cells Cultured

The dynamic development of the space industry makes space flights more accessible and opens up new opportunities for biological research to better understand cell physiology under real microgravity. Whereas specialized studies in space remain out of our reach, preliminary experiments can be performed on Earth under simulated microgravity (sµg). Based on this concept, we used a 3D-clinostat (3D-C) to analyze the effect of short exposure to sµg on human keratinocytes HaCaT and melanoma cells A375 cultured on all-glass Lab-on-a-Chip (LOC). Our preliminary studies included viability evaluation, mitochondrial and caspase activity, and proliferation assay, enabling us to determine the effect of sµg on human cells. By comparing the results concerning cells cultured on LOCs and standard culture dishes, we were able to confirm the biocompatibility of all-glass LOCs and their potential application in microgravity research on selected human cell lines. Our studies revealed that HaCaT and A375 cells are susceptible to simulated microgravity; however, we observed an increased caspase activity and a decrease of proliferation in cancer cells cultured on LOCs in comparison to standard cell cultures. These results are an excellent basis to conduct further research on the possible application of LOCs systems in cancer research in space.

scholarly journals Feedback Regulation of O-GlcNAc Transferase through Translation Control to Maintain Intracellular O-GlcNAc Homeostasis

2021 ◽  
Vol 22 (7) ◽  
pp. 3463
Author(s):  
Chia-Hung Lin ◽  
Chen-Chung Liao ◽  
Mei-Yu Chen ◽  
Teh-Ying Chou
Keyword(s):  
Molecular Mechanisms ◽  
Mrna Level ◽  
Feedback Regulation ◽  
Translation Initiation Factor ◽  
Initiation Factor ◽  
Cell Physiology ◽  
Hydroxyl Groups ◽  
Post Translational Modification ◽  
Translation Control ◽  
Glcnac Transferase

Protein O-GlcNAcylation is a dynamic post-translational modification involving the attachment of N-acetylglucosamine (GlcNAc) to the hydroxyl groups of Ser/Thr residues on numerous nucleocytoplasmic proteins. Two enzymes are responsible for O-GlcNAc cycling on substrate proteins: O-GlcNAc transferase (OGT) catalyzes the addition while O-GlcNAcase (OGA) helps the removal of GlcNAc. O-GlcNAcylation modifies protein functions; therefore, dysregulation of O-GlcNAcylation affects cell physiology and contributes to pathogenesis. To maintain homeostasis of cellular O-GlcNAcylation, there exists feedback regulation of OGT and OGA expression responding to fluctuations of O-GlcNAc levels; yet, little is known about the molecular mechanisms involved. In this study, we investigated the O-GlcNAc-feedback regulation of OGT and OGA expression in lung cancer cells. Results suggest that, upon alterations in O-GlcNAcylation, the regulation of OGA expression occurs at the mRNA level and likely involves epigenetic mechanisms, while modulation of OGT expression is through translation control. Further analyses revealed that the eukaryotic translation initiation factor 4E-binding protein 1 (4E-BP1) contributes to the downregulation of OGT induced by hyper-O-GlcNAcylation; the S5A/S6A O-GlcNAcylation-site mutant of 4E-BP1 cannot support this regulation, suggesting an important role of O-GlcNAcylation. The results provide additional insight into the molecular mechanisms through which cells may fine-tune intracellular O-GlcNAc levels to maintain homeostasis.

Eukaryotic protein uS19: a component of the decoding site of ribosomes and a player in human diseases

2021 ◽  
Vol 478 (5) ◽  
pp. 997-1008
Author(s):  
Dmitri Graifer ◽  
Galina Karpova
Keyword(s):  
Ribosome Biogenesis ◽  
Lymphocytic Leukemia ◽  
Human Diseases ◽  
Tumor Suppressor P53 ◽  
Translational Fidelity ◽  
Gene Encoding ◽  
Ribosomal Subunits ◽  
Translational Machinery ◽  
Diamond Blackfan Anemia ◽  
Ribosomal Function

Proteins belonging to the universal ribosomal protein (rp) uS19 family are constituents of small ribosomal subunits, and their conserved globular parts are involved in the formation of the head of these subunits. The eukaryotic rp uS19 (previously known as S15) comprises a C-terminal extension that has no homology in the bacterial counterparts. This extension is directly implicated in the formation of the ribosomal decoding site and thereby affects translational fidelity in a manner that has no analogy in bacterial ribosomes. Another eukaryote-specific feature of rp uS19 is its essential participance in the 40S subunit maturation due to the interactions with the subunit assembly factors required for the nuclear exit of pre-40S particles. Beyond properties related to the translation machinery, eukaryotic rp uS19 has an extra-ribosomal function concerned with its direct involvement in the regulation of the activity of an important tumor suppressor p53 in the Mdm2/Mdmx-p53 pathway. Mutations in the RPS15 gene encoding rp uS19 are linked to diseases (Diamond Blackfan anemia, chronic lymphocytic leukemia and Parkinson's disease) caused either by defects in the ribosome biogenesis or disturbances in the functioning of ribosomes containing mutant rp uS19, likely due to the changed translational fidelity. Here, we review currently available data on the involvement of rp uS19 in the operation of the translational machinery and in the maturation of 40S subunits, on its extra-ribosomal function, and on relationships between mutations in the RPS15 gene and certain human diseases.

scholarly journals Neuronal ribosomes exhibit dynamic and context-dependent exchange of ribosomal proteins

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Claudia M. Fusco ◽  
Kristina Desch ◽  
Aline R. Dörrbaum ◽  
Mantian Wang ◽  
Anja Staab ◽  
...  
Keyword(s):  
Ribosomal Proteins ◽  
Ribosome Biogenesis ◽  
Ribosome Profiling ◽  
Metabolic Labeling ◽  
Local Protein Synthesis ◽  
Translational Machinery ◽  
Neuronal Synapses ◽  
Cellular Environment ◽  
Neuronal Processes ◽  
Local Protein

AbstractOwing to their morphological complexity and dense network connections, neurons modify their proteomes locally, using mRNAs and ribosomes present in the neuropil (tissue enriched for dendrites and axons). Although ribosome biogenesis largely takes place in the nucleus and perinuclear region, neuronal ribosomal protein (RP) mRNAs have been frequently detected remotely, in dendrites and axons. Here, using imaging and ribosome profiling, we directly detected the RP mRNAs and their translation in the neuropil. Combining brief metabolic labeling with mass spectrometry, we found that a group of RPs rapidly associated with translating ribosomes in the cytoplasm and that this incorporation was independent of canonical ribosome biogenesis. Moreover, the incorporation probability of some RPs was regulated by location (neurites vs. cell bodies) and changes in the cellular environment (following oxidative stress). Our results suggest new mechanisms for the local activation, repair and/or specialization of the translational machinery within neuronal processes, potentially allowing neuronal synapses a rapid means to regulate local protein synthesis.

scholarly journals Arabinogalactan Proteins in Plant Roots – An Update on Possible Functions

2021 ◽  
Vol 12 ◽  
Author(s):  
Dagmar Hromadová ◽  
Aleš Soukup ◽  
Edita Tylová
Keyword(s):  
Cell Wall ◽  
Regulatory Networks ◽  
Developmental Plasticity ◽  
Molecular Mechanisms ◽  
Arabinogalactan Proteins ◽  
Cellular Level ◽  
Environmental Response ◽  
Essential Components ◽  
Surface Signaling ◽  
Cell Surface Signaling

Responsiveness to environmental conditions and developmental plasticity of root systems are crucial determinants of plant fitness. These processes are interconnected at a cellular level with cell wall properties and cell surface signaling, which involve arabinogalactan proteins (AGPs) as essential components. AGPs are cell-wall localized glycoproteins, often GPI-anchored, which participate in root functions at many levels. They are involved in cell expansion and differentiation, regulation of root growth, interactions with other organisms, and environmental response. Due to the complexity of cell wall functional and regulatory networks, and despite the large amount of experimental data, the exact molecular mechanisms of AGP-action are still largely unknown. This dynamically evolving field of root biology is summarized in the present review.

scholarly journals Modeling acute ethanol-induced impairment with gastric organoids

2021 ◽  
Author(s):  
Wanjuan Wang ◽  
Ying Zhao ◽  
Zeqi Su ◽  
Fuhao Chu ◽  
Tao Li ◽  
...  
Keyword(s):  
Gastric Carcinoma ◽  
Molecular Mechanisms ◽  
Apical Membrane ◽  
Parietal Cells ◽  
Basic Medium ◽  
Cell Physiology ◽  
Membrane Cytoskeleton ◽  
Acute Ethanol ◽  
Functional Consequences ◽  
Gastric Parietal Cells

Abstract Background: Ethanol has been linked to atrophic gastritis and gastric carcinoma. Although it is well known that ethanol can result in hypochlorhydria, the molecular mechanisms underlying this phenomenon remain poorly understood.Results: Here we used gastric organoids to show that ethanol permeabilized the apical membrane of gastric parietal cells and induced ezrin hypochlorhydria. The functional consequences of ethanol on parietal cell physiology were studied using organoids. Gastric organoids were pre-incubated in the basic medium or with EGTA or E64 , and incubated at 37℃ in either medium alone, or medium containing 6% ethanol. We assessed ezrin proteolysis. Ethanol permeabilization induced activation of calpainⅠand subsequent proteolysis of ezrin, which resulted in the liberation of ezrin from the apical membrane of the parietal cells. Significantly, expression of calpain-resistant ezrin restored the functional activity of parietal cells in the presence of ethanol.Conclusion: Taken together, our data indicated that ethanol disrupted the apical membrane-cytoskeleton interactions in gastric parietal cells and thereby caused hypochlorhydria.

scholarly journals Trpm5 channels encode bistability of spinal motoneurons and ensure motor control of hindlimbs in mice

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Rémi Bos ◽  
Benoît Drouillas ◽  
Mouloud Bouhadfane ◽  
Emilie Pecchi ◽  
Virginie Trouplin ◽  
...  
Keyword(s):  
Spinal Cord ◽  
Endoplasmic Reticulum ◽  
Molecular Mechanisms ◽  
Central Pattern Generators ◽  
Cellular Level ◽  
Spinal Motoneurons ◽  
Plateau Potential ◽  
Serca Pump ◽  
Pattern Generators ◽  
Postural Tone

AbstractBistable motoneurons of the spinal cord exhibit warmth-activated plateau potential driven by Na+ and triggered by a brief excitation. The thermoregulating molecular mechanisms of bistability and their role in motor functions remain unknown. Here, we identify thermosensitive Na+-permeable Trpm5 channels as the main molecular players for bistability in mouse motoneurons. Pharmacological, genetic or computational inhibition of Trpm5 occlude bistable-related properties (slow afterdepolarization, windup, plateau potentials) and reduce spinal locomotor outputs while central pattern generators for locomotion operate normally. At cellular level, Trpm5 is activated by a ryanodine-mediated Ca2+ release and turned off by Ca2+ reuptake through the sarco/endoplasmic reticulum Ca2+-ATPase (SERCA) pump. Mice in which Trpm5 is genetically silenced in most lumbar motoneurons develop hindlimb paresis and show difficulties in executing high-demanding locomotor tasks. Overall, by encoding bistability in motoneurons, Trpm5 appears indispensable for producing a postural tone in hindlimbs and amplifying the locomotor output.

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