Mapping Sub-Cellular Protein Aggregates and Lipid Inclusions Using Synchrotron Radiation ATR-FTIR Microscopy

The Analyst ◽  
2021 ◽  
Author(s):  
David Hartnell ◽  
Ashley Hollings ◽  
Anna Maria Ranieri ◽  
Hum Bahadur Lamichhane ◽  
Thomas Becker ◽  
...  
Keyword(s):  
Biological Sciences ◽  
Synchrotron Radiation ◽  
Biochemical Markers ◽  
Protein Aggregates ◽  
Cellular Protein ◽  
Cellular Level ◽  
Cell Physiology ◽  
Ftir Microscopy ◽  
Lipid Inclusions

Visualising direct biochemical markers of cell physiology and disease pathology at the sub-cellular level is an ongoing challenge in the biological sciences. A suite of microscopies exists to either visualise...

scholarly journals Disaggregases, molecular chaperones that resolubilize protein aggregates

2015 ◽  
Vol 87 (2 suppl) ◽  
pp. 1273-1292 ◽  
Author(s):  
David Z. Mokry ◽  
Josielle Abrahão ◽  
Carlos H.I. Ramos
Keyword(s):  
Heat Shock ◽  
Molecular Chaperones ◽  
Protein Function ◽  
Protein Aggregates ◽  
Cell Physiology ◽  
Biological Processes ◽  
Loss Of Function ◽  
Prion Propagation ◽  
Shock Proteins

The process of folding is a seminal event in the life of a protein, as it is essential for proper protein function and therefore cell physiology. Inappropriate folding, or misfolding, can not only lead to loss of function, but also to the formation of protein aggregates, an insoluble association of polypeptides that harm cell physiology, either by themselves or in the process of formation. Several biological processes have evolved to prevent and eliminate the existence of non-functional and amyloidogenic aggregates, as they are associated with several human pathologies. Molecular chaperones and heat shock proteins are specialized in controlling the quality of the proteins in the cell, specifically by aiding proper folding, and dissolution and clearance of already formed protein aggregates. The latter is a function of disaggregases, mainly represented by the ClpB/Hsp104 subfamily of molecular chaperones, that are ubiquitous in all organisms but, surprisingly, have no orthologs in the cytosol of metazoan cells. This review aims to describe the characteristics of disaggregases and to discuss the function of yeast Hsp104, a disaggregase that is also involved in prion propagation and inheritance.

scholarly journals Protein Aggregation is Associated with Acinetobacter baumannii Desiccation Tolerance

2020 ◽  
Vol 8 (3) ◽  
pp. 343 ◽  
Author(s):  
Xun Wang ◽  
Cody G. Cole ◽  
Cory D. DuPai ◽  
Bryan W. Davies
Keyword(s):  
Acinetobacter Baumannii ◽  
Desiccation Tolerance ◽  
Bacterial Pathogen ◽  
Protein Aggregates ◽  
Cellular Protein ◽  
Aggregate Formation ◽  
Growth Phases ◽  
Protein Aggregate ◽  
Factors Influencing ◽  
Cellular Aggregates

Desiccation tolerance has been implicated as an important characteristic that potentiates the spread of the bacterial pathogen Acinetobacter baumannii on dry surfaces. Here we explore several factors influencing desiccation survival of A. baumannii. At the macroscale level, we find that desiccation tolerance is influenced by cell density and growth phase. A transcriptome analysis indicates that desiccation represents a unique state for A. baumannii compared to commonly studied growth phases and strongly influences pathways responsible for proteostasis. Remarkably, we find that an increase in total cellular protein aggregates, which is often considered deleterious, correlates positively with the ability of A. baumannii to survive desiccation. We show that inducing protein aggregate formation prior to desiccation increases survival and, importantly, that proteins incorporated into cellular aggregates can retain activity. Our results suggest that protein aggregates may promote desiccation tolerance in A. baumannii through preserving and protecting proteins from damage during desiccation until rehydration occurs.

scholarly journals Editorial Report for 1980

1981 ◽  
Vol 34 (1) ◽  
pp. 1
Keyword(s):  
Biological Sciences ◽  
Reproductive Biology ◽  
Australian Journal ◽  
Cell Physiology ◽  
Research Papers ◽  
Review Articles

In 1980, the Australian Journal of Biological Sciences published 67 research papers and three review articles in six issues in the following disciplines: biochemistry (23 papers), endocrinology and reproductive biology (15), genetics (10), physiology (9), microbiology (9) and cell physiology and ultrastructure (4). There has been an increase in biochemical and microbiological papers over the previous year.

scholarly journals The study of efficiency of endogenous and exogenous preventive methods of tooth enamel remineralisation by FTIR microscopy using synchrotron radiation

2016 ◽  
Vol 741 ◽  
pp. 012054 ◽  
Author(s):  
D L Goloshchapov ◽  
V M Kashkarov ◽  
P V Seredin ◽  
Y A Ippolitov ◽  
Y A Plotnikova ◽  
...  
Keyword(s):  
Synchrotron Radiation ◽  
Tooth Enamel ◽  
Ftir Microscopy ◽  
Preventive Methods

scholarly journals Drosophila egg-derived tyrosine phosphatase (EDTP): a novel target for improved survivorship to prolonged anoxia and cellular protein aggregates

2018 ◽  
Author(s):  
Chengfeng Xiao ◽  
Shuang Qiu ◽  
Xiao Li ◽  
Dan-Ju Luo ◽  
Gong-Ping Liu
Keyword(s):  
Hippocampal Neurons ◽  
Genetic Disorder ◽  
Tyrosine Phosphatase ◽  
Protein Aggregates ◽  
Cellular Protein ◽  
Muscle Performance ◽  
Homologous Gene ◽  
Sprague Dawley ◽  
Tissue Specific ◽  
Novel Approach

AbstractDrosophila egg-derived tyrosine phosphatase (EDTP), a lipid phosphatase that removes 3-position phosphate at the inositol ring, has dual functions in the oogenesis and the muscle performance during adult stages. A mammalian homologous gene MTMR14, which encodes the myotubularin-related protein 14, negatively regulates autophagy. Mutation of EDTP/MTMR14, however, causes at least three deleterious consequences: (1) lethality in the early embryogenesis in Drosophila; (2) “jumpy” phenotype with apparently impaired motor functions; and (3) association with a rare genetic disorder called centronuclear myopathy. Here we show that flies carrying a heterozygous EDTP mutation had increased survivorship to prolonged anoxia; tissue-specific downregulation of EDTP in non-muscle tissues, particularly motoneurons, extended the lifespan; and tissue-specific downregulation of EDTP in motoneurons improved the survivorship to beta-amyloid peptides (Aβ42) and polyglutamine (polyQ) protein aggregates. MTMR14 expression was evident in the hippocampus and cortex in C57BL/6J and APP/PS1 mice. Compared with C57BL/6J mice, APP/PS1 mice had reduced MTMR14 in the cortex but not in the hippocampus. Hippocampal expression of MTMR14 was increased and plateaued at 9-17 months compared with 2-6 months in C57BL/6J mice. Aβ42 treatment increased the expression of MTMR14 in the primarily cultured hippocampal neurons of Sprague/Dawley rats and mouse Neuro2a neuroblasts. We demonstrated a novel approach of tissue-specific manipulation of the disease-associated gene EDTP/MTMR14 for lifespan extension and the improvement of survivorship to cellular protein aggregates.

scholarly journals Evolved, Selective Erasers of Distinct Lysine Acylations

2019 ◽  
Author(s):  
Martin Spinck ◽  
Maria Ecke ◽  
Raphael Gasper ◽  
Heinz Neumann
Keyword(s):  
Conformational Changes ◽  
Metabolic Diseases ◽  
Great Part ◽  
Cellular Level ◽  
Cell Physiology ◽  
Post Translational Modification ◽  
Physiological Processes ◽  
Lysine Residues ◽  
Small Set ◽  
Lysine Deacetylases

AbstractLysine acetylation, including related lysine modifications such as butyrylation and crotonylation, is a widespread post-translational modification with important roles in many important physiological processes. However, uncovering the regulatory mechanisms that govern the reverse process, deacylation, has been challenging to address, in great part because the small set of lysine deacetylases (KDACs) that remove the modifications are promiscuous in their substrate and acylation-type preference. This lack of selectivity hinders a broader understanding of how deacylation is regulated at the cellular level and how it is correlated with lysine deacylation-related diseases. To facilitate the dissection of KDACs with respect to substrate specificity and modification type, it would be beneficial to re-engineer KDACs to be selective towards a given substrate and/or modification. To dissect the differential contributions of various acylations to cell physiology, we developed a novel directed evolution approach to create selective KDAC variants that are up to 400-fold selective towards butyryl- over crotonyl-lysine substrates. Structural analyses of this non-promiscuous KDAC revealed unprecedented insights regarding the conformational changes mediating the gain in specificity. As a second case study to illustrate the power of this approach, we re-engineer the human SirT1 to increase its selectivity towards acetylated versus crotonylated substrates. These new enzymes, as well as the generic approach that we report here, will greatly facilitate the dissection of the differential roles of lysine acylation in cell physiology.Significance StatementAcetylation of lysine residues features numerous roles in diverse physiological processes and correlates with the manifestation of metabolic diseases, cancer and ageing. The already huge diversity of the acetylome is multiplied by variations in the types of acylation. This complexity is in stark contrast to the small set of lysine deacetylases (KDACs) present in human cells, anticipating a pronounced substrate promiscuity.We device a strategy to tackle this disarray by creating KDAC variants with increased selectivity towards particular types of lysine acylations using a novel selection system. The variants facilitate the dissection of the differential contributions of particular acylations to gene expression, development and disease. Our structural analyses shed light on the mechanism of substrate discrimination by Sirtuin-type KDACs.

scholarly journals Translational regulation of environmental adaptation in bacteria

2020 ◽  
Vol 295 (30) ◽  
pp. 10434-10445 ◽  
Author(s):  
Rodney Tollerson ◽  
Michael Ibba
Keyword(s):  
Gene Expression ◽  
Translation Initiation ◽  
Environmental Changes ◽  
Specific Protein ◽  
Cellular Protein ◽  
Nutrient Concentrations ◽  
Cell Physiology ◽  
Translation Rate ◽  
Control Of Gene Expression ◽  
Cellular Environment

Bacteria must rapidly respond to both intracellular and environmental changes to survive. One critical mechanism to rapidly detect and adapt to changes in environmental conditions is control of gene expression at the level of protein synthesis. At each of the three major steps of translation—initiation, elongation, and termination—cells use stimuli to tune translation rate and cellular protein concentrations. For example, changes in nutrient concentrations in the cell can lead to translational responses involving mechanisms such as dynamic folding of riboswitches during translation initiation or the synthesis of alarmones, which drastically alter cell physiology. Moreover, the cell can fine-tune the levels of specific protein products using programmed ribosome pausing or inducing frameshifting. Recent studies have improved understanding and revealed greater complexity regarding long-standing paradigms describing key regulatory steps of translation such as start-site selection and the coupling of transcription and translation. In this review, we describe how bacteria regulate their gene expression at the three translational steps and discuss how translation is used to detect and respond to changes in the cellular environment. Finally, we appraise the costs and benefits of regulation at the translational level in bacteria.

scholarly journals Differences and Similarities in Viral Life Cycle Progression and Host Cell Physiology after Infection of Human Dendritic Cells with Modified Vaccinia Virus Ankara and Vaccinia Virus

2006 ◽  
Vol 80 (17) ◽  
pp. 8469-8481 ◽  
Author(s):  
Ann Chahroudi ◽  
David A. Garber ◽  
Patrick Reeves ◽  
Luzheng Liu ◽  
Daniel Kalman ◽  
...  
Keyword(s):  
Dendritic Cells ◽  
Immune Responses ◽  
Vaccinia Virus ◽  
Viral Vector ◽  
Cellular Protein ◽  
Distinct Pattern ◽  
Cell Physiology ◽  
Human Immune System ◽  
Modified Vaccinia Virus Ankara ◽  
Human Dendritic Cells

ABSTRACT Modified vaccinia virus Ankara (MVA) is an attenuated strain of vaccinia virus (VV) that has attracted significant attention as a candidate viral vector vaccine for immunization against infectious diseases and treatment of malignancies. Although MVA is unable to replicate in most nonavian cells, vaccination with MVA elicits immune responses that approximate those seen after the administration of replication-competent strains of VV. However, the mechanisms by which these viruses elicit immune responses and the determinants of their relative immunogenicity are incompletely understood. Studying the interactions of VV and MVA with cells of the human immune system may elucidate these mechanisms, as well as provide a rational basis for the further enhancement of the immunogenicity of recombinant MVA vectors. Toward this end, we investigated the consequences of MVA or VV infection of human dendritic cells (DCs), key professional antigen-presenting cells essential for the generation of immune responses. We determined that a block to the formation of intracellular viral replication centers results in abortive infection of DCs with both VV and MVA. MVA inhibited cellular protein synthesis more rapidly than VV and displayed a distinct pattern of viral protein expression in infected DCs. MVA also induced apoptosis in DCs more rapidly than VV, and DC apoptosis after MVA infection was associated with an accelerated decline in the levels of intracellular Bcl-2 and Bcl-XL. These findings suggest that antigen presentation pathways may contribute differentially to the immunogenicity of VV and MVA and that targeted modifications of virus-induced DC apoptosis may further increase the immunogenicity of MVA-vectored vaccines.

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