scholarly journals Pathogenesis of Mucopolysaccharidoses, an Update

2020 ◽  
Vol 21 (7) ◽  
pp. 2515 ◽  
Author(s):  
Simona Fecarotta ◽  
Antonietta Tarallo ◽  
Carla Damiano ◽  
Nadia Minopoli ◽  
Giancarlo Parenti
Keyword(s):  
Clinical Manifestations ◽  
Cellular Functions ◽  
Cellular Processes ◽  
Cellular Events ◽  
New Information ◽  
New Vision ◽  
And Function ◽  
And Oxidative Stress ◽  
Novel Therapeutic

The recent advancements in the knowledge of lysosomal biology and function have translated into an improved understanding of the pathophysiology of mucopolysaccharidoses (MPSs). The concept that MPS manifestations are direct consequences of lysosomal engorgement with undegraded glycosaminoglycans (GAGs) has been challenged by new information on the multiple biological roles of GAGs and by a new vision of the lysosome as a signaling hub involved in many critical cellular functions. MPS pathophysiology is now seen as the result of a complex cascade of secondary events that lead to dysfunction of several cellular processes and pathways, such as abnormal composition of membranes and its impact on vesicle fusion and trafficking; secondary storage of substrates; impairment of autophagy; impaired mitochondrial function and oxidative stress; dysregulation of signaling pathways. The characterization of this cascade of secondary cellular events is critical to better understand the pathophysiology of MPS clinical manifestations. In addition, some of these pathways may represent novel therapeutic targets and allow for the development of new therapies for these disorders.

Establishing a model to demonstrate physical and mathematical properties of chromatin fibres in fission yeast cells - Research in the Molecular Biophysics Lab at Hiroshima University

Impact ◽  
2018 ◽  
Vol 2018 (3) ◽  
pp. 89-91
Author(s):  
Shin-ichi Tate
Keyword(s):  
Molecular Biology ◽  
Yeast Cells ◽  
Molecular Architecture ◽  
Ministry Of Education ◽  
Cellular Functions ◽  
Sports Science ◽  
Cellular Events ◽  
And Function ◽  
Education Culture ◽  
Open The Doors

The field of molecular biology has provided great insights into the structure and function of key molecules. Thanks to this area of research, we can now grasp the biological details of DNA and have characterised an enormous number of molecules in massive data bases. These 'biological periodic tables' have allowed scientists to connect molecules to particular cellular events, furthering scientific understanding of biological processes. However, molecular biology has yet to answer questions regarding 'higher-order' molecular architecture, such as that of chromatin. Chromatin is the molecular material that serves as the building block for chromosomes, the structures that carry an organism's genetic information inside of the cell's nucleus. Understanding the physical properties of chromatin is crucial in developing a more thorough picture of how chromatin's structure relate to its key cellular functions. Moreover, by establishing a physical model of chromatin, scientists will be able to open the doors into the true inner workings of the cell nucleus. Professor Shin-ichi Tate and his team of researchers at Hiroshima University's Research Center for the Mathematics on Chromatin Live Dynamics (RcMcD), are attempting to do just that. Through a five-year grant funded by the Platform for Dynamic Approaches to Living Systems from the Ministry of Education, Culture, Sports, Science and Technology, Tate is aiming to gain a clearer understanding of the structure and dynamics of chromatin.

scholarly journals Bend, Push, Stretch: Remarkable Structure and Mechanics of Single Intermediate Filaments and Meshworks

Cells ◽  
2021 ◽  
Vol 10 (8) ◽  
pp. 1960
Author(s):  
K. Tanuj Sapra ◽  
Ohad Medalia
Keyword(s):  
Intermediate Filaments ◽  
Eukaryotic Cell ◽  
Coiled Coils ◽  
Cellular Functions ◽  
Mechanical Pressure ◽  
Mechanical Feature ◽  
Cellular Processes ◽  
Nuclear Lamins ◽  
Filament Networks ◽  
And Function

The cytoskeleton of the eukaryotic cell provides a structural and functional scaffold enabling biochemical and cellular functions. While actin and microtubules form the main framework of the cell, intermediate filament networks provide unique mechanical properties that increase the resilience of both the cytoplasm and the nucleus, thereby maintaining cellular function while under mechanical pressure. Intermediate filaments (IFs) are imperative to a plethora of regulatory and signaling functions in mechanotransduction. Mutations in all types of IF proteins are known to affect the architectural integrity and function of cellular processes, leading to debilitating diseases. The basic building block of all IFs are elongated α-helical coiled-coils that assemble hierarchically into complex meshworks. A remarkable mechanical feature of IFs is the capability of coiled-coils to metamorphize into β-sheets under stress, making them one of the strongest and most resilient mechanical entities in nature. Here, we discuss structural and mechanical aspects of IFs with a focus on nuclear lamins and vimentin.

scholarly journals Label-free methods for optical in vitro characterization of protein–protein interactions

2021 ◽  
Author(s):  
Fabian Soltermann ◽  
Weston B. Struwe ◽  
Philipp Kukura
Keyword(s):  
Protein Interactions ◽  
Label Free ◽  
Protein Protein Interactions ◽  
Cellular Processes ◽  
P Protein ◽  
In Vitro Characterization ◽  
And Function

Protein–protein interactions are involved in the regulation and function of the majority of cellular processes.

scholarly journals Protein manipulation using single copies of short peptide tags in cultured cells and in Drosophila melanogaster

2020 ◽  
Author(s):  
M. Alessandra Vigano ◽  
Clara-Maria Ell ◽  
Manuela MM Kustermann ◽  
Gustavo Aguilar ◽  
Shinya Matsuda ◽  
...  
Keyword(s):  
Cultured Cells ◽  
Single Copy ◽  
Specific Protein ◽  
Cellular Functions ◽  
Cellular Processes ◽  
Peptide Tags ◽  
Genetic Technologies ◽  
Protein Binders ◽  
And Function

AbstractCellular development and specialized cellular functions are regulated processes which rely on highly dynamic molecular interactions among proteins, distributed in all cell compartments. Analysis of these interactions and their mechanisms of action has been one of the main topics in cellular and developmental research over the last fifty years. Studying and understanding the functions of proteins of interest (POIs) has been mostly achieved by their alteration at the genetic level and the analysis of the phenotypic changes generated by these alterations. Although genetic and reverse genetic technologies contributed to the vast majority of information and knowledge we have gathered so far, targeting specific interactions of POIs in a time- and space-controlled manner or analyzing the role of POIs in dynamic cellular processes such as cell migration or cell division would require more direct approaches. The recent development of specific protein binders, which can be expressed and function intracellularly, together with several improvements in synthetic biology techniques, have contributed to the creation of a new toolbox for direct protein manipulations. We selected a number of short tag epitopes for which protein binders from different scaffolds have been developed and tested whether these tags can be bound by the corresponding protein binders in living cells when they are inserted in a single copy in a POI. We indeed find that in all cases, a single copy of a short tag allows protein binding and manipulation. Using Drosophila, we also find that single short tags can be recognized and allow degradation and relocalization of POIs in vivo.

scholarly journals Structure and Function of Mitochondria-Associated Endoplasmic Reticulum Membranes (MAMs) and Their Role in Cardiovascular Diseases

2021 ◽  
Vol 2021 ◽  
pp. 1-19
Author(s):  
Yi Luan ◽  
Ying Luan ◽  
Rui-Xia Yuan ◽  
Qi Feng ◽  
Xing Chen ◽  
...  
Keyword(s):  
Endoplasmic Reticulum ◽  
Vascular Endothelial Cells ◽  
Mitochondrial Dynamics ◽  
Cellular Functions ◽  
Cellular Processes ◽  
Unfolded Protein ◽  
Associated Proteins ◽  
Apoptosis And Inflammation ◽  
And Function ◽  
Protein Response

Abnormal function of suborganelles such as mitochondria and endoplasmic reticulum often leads to abnormal function of cardiomyocytes or vascular endothelial cells and cardiovascular disease (CVD). Mitochondria-associated membrane (MAM) is involved in several important cellular functions. Increasing evidence shows that MAM is involved in the pathogenesis of CVD. MAM mediates multiple cellular processes, including calcium homeostasis regulation, lipid metabolism, unfolded protein response, ROS, mitochondrial dynamics, autophagy, apoptosis, and inflammation, which are key risk factors for CVD. In this review, we discuss the structure of MAM and MAM-associated proteins, their role in CVD progression, and the potential use of MAM as the therapeutic targets for CVD treatment.

scholarly journals Characterization of Mitochondrial GSH Transporters and Their Role in RPE Protection

2018 ◽  
Author(s):  
Mo Wang ◽  
Ling-ing Lau ◽  
Parameswaran G. Sreekumar ◽  
Christine Spee ◽  
Lin Liu ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Retinal Pigment ◽  
Retinal Pigment Epithelial Cells ◽  
Age Related Macular Degeneration ◽  
Ocular Tissues ◽  
Age Related ◽  
And Function ◽  
And Oxidative Stress ◽  
Pigment Epithelial Cells

Mitochondrial dysfunction and oxidative stress are thought to be relevant to the pathogenesis of age-related macular degeneration (AMD). Glutathione (GSH) homeostasis fulfills a number of important roles in mitochondria, such as maintenance of mitochondrial DNA and respiratory competency of cells. Although the transport of mitochondrial GSH (mGSH) is not fully understood, increasing evidence from non-ocular tissues suggests that OGC (2-oxoglutarate carrier, SLC25A11) and DIC (dicarboxylate carrier, SLC25A10) are involved in mGSH transport. However, whether OGC and DIC mediate the transfer of GSH into the mitochondria of retinal pigment epithelial cells (RPE) remains unknown. Thus, we investigated the expression, localization, and function of OGC and DIC in human RPE (hRPE) in relation to oxidative stress and GSH. Both OGC and DIC are expressed in hRPE and are localized in mitochondria. We also found a dose and time-dependent decrease of OGC and DIC expression under oxidative stress and increased expression in polarized RPE. Our data show that the downregulation of OGC and DIC resulted in increased apoptosis and mGSH depletion which can be overcome by co-treatment with GSH-MEE. These findings suggest that overexpression of OGC and DIC may be an effective strategy to decrease susceptibility to mitochondrial toxicants by elevation of mGSH.

scholarly journals Ceramide structure dictates glycosphingolipid nanodomain assembly and function

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Senthil Arumugam ◽  
Stefanie Schmieder ◽  
Weria Pezeshkian ◽  
Ulrike Becken ◽  
Christian Wunder ◽  
...  
Keyword(s):  
Plasma Membrane ◽  
Acyl Chain ◽  
Cholera Toxin B Subunit ◽  
Cellular Functions ◽  
Toxin B ◽  
Cellular Processes ◽  
B Subunit ◽  
Outer Leaflet ◽  
And Function ◽  
Nanodomain Structure

AbstractGangliosides in the outer leaflet of the plasma membrane of eukaryotic cells are essential for many cellular functions and pathogenic interactions. How gangliosides are dynamically organized and how they respond to ligand binding is poorly understood. Using fluorescence anisotropy imaging of synthetic, fluorescently labeled GM1 gangliosides incorporated into the plasma membrane of living cells, we found that GM1 with a fully saturated C16:0 acyl chain, but not with unsaturated C16:1 acyl chain, is actively clustered into nanodomains, which depends on membrane cholesterol, phosphatidylserine and actin. The binding of cholera toxin B-subunit (CTxB) leads to enlarged membrane domains for both C16:0 and C16:1, owing to binding of multiple GM1 under a toxin, and clustering of CTxB. The structure of the ceramide acyl chain still affects these domains, as co-clustering with the glycosylphosphatidylinositol (GPI)-anchored protein CD59 occurs only when GM1 contains the fully saturated C16:0 acyl chain, and not C16:1. Thus, different ceramide species of GM1 gangliosides dictate their assembly into nanodomains and affect nanodomain structure and function, which likely underlies many endogenous cellular processes.

scholarly journals Neutrophil Functions in Periodontal Homeostasis

2016 ◽  
Vol 2016 ◽  
pp. 1-9 ◽  
Author(s):  
Ricarda Cortés-Vieyra ◽  
Carlos Rosales ◽  
Eileen Uribe-Querol
Keyword(s):  
Bone Loss ◽  
Immune Cells ◽  
Oral Bacteria ◽  
Innate Immune ◽  
Innate Immune Cells ◽  
Therapeutic Approaches ◽  
New Information ◽  
Inflammatory State ◽  
And Function ◽  
Novel Therapeutic

Oral tissues are constantly exposed to damage from the mechanical effort of eating and to microorganisms, mostly bacteria. In healthy gingiva tissue remodeling and a balance between bacteria and innate immune cells are maintained. However, excess of bacteria biofilm (plaque) creates an inflammation state that recruits more immune cells, mainly neutrophils to the gingiva. Neutrophils create a barrier for bacteria to reach inside tissues. When neutrophils are insufficient, bacteria thrive causing more inflammation that has been associated with systemic effects on other conditions such as atherosclerosis, diabetes, and cancer. But paradoxically when neutrophils persist, they can also promote a chronic inflammatory state that leads to periodontitis, a condition that leads to damage of the bone-supporting tissues. In periodontitis, bone loss is a serious complication. How a neutrophil balance is needed for maintaining healthy oral tissues is the focus of this review. We present recent evidence on how alterations in neutrophil number and function can lead to inflammatory bone loss, and how some oral bacteria signal neutrophils to block their antimicrobial functions and promote an inflammatory state. Also, based on this new information, novel therapeutic approaches are discussed.

scholarly journals Characterization of the Regulation and Function of Phosphatidylinositol 3,5-Bisphosphate

2021 ◽  
Author(s):  
Shannon Cheuk Ying Ho
Keyword(s):  
Membrane Trafficking ◽  
Adaptor Protein ◽  
Cellular Functions ◽  
Lipid Kinase ◽  
Cellular Processes ◽  
Lipid Phosphatase ◽  
Tooth Type ◽  
And Function ◽  
Endocytic Compartments ◽  
Lysosomal Acidification

PtdIns(3,5)P2 is a low abundance phosphoinositide that is involved in a variety of cellular processes. Most notably, PtdIns(3,5)P2 is known to regulate vacuolar/lysosomal morphology. Deficiency in PtdIns(3,5)P2 results in enlargement of the yeast vacuole and, an extensive vacuolation of the late endocytic compartments in higher eukaryotes (1, 2). In addition, PtdIns(3,5)P2 is also involved in cellular functions including membrane trafficking, autophagy, and vacuolar/lysosomal acidification. However, the current study provided evidence that shows that the vacuole/lysosomes of PtdIns(3,5)P2-deficient cells remain acidic. Hence, PtdIns(3,5)P2 may not have a role in steady-state vacuolar/lysosomal acidification. PtdIns(3,5)P2 is synthesized by the Fab1 lipid kinase and degraded by the antagonistic Fig4 lipid phosphatase. Vac14, an adaptor protein, is known to interact with both Fab1 and Fig4 to form a complex on the vacuolar membrane. This study demonstrated that Vac14 is required to form a homodimer for its interaction with Fig4 and Fab1. In addition, formation of the homodimer is necessary for regulation of PtdIns(3,5)P2. Mutations in human Vac14 and Fig4 has been identified in patients with neurodegenerative diseases, such as amyotrophic lateral sclerosis and Charcot-Marie-Tooth Type 4J (3, 4). This study provides an important stepping stone in characterizing the regulatory mechanism and understanding the function of PtdIns(3,5)P2

scholarly journals Characterization of the Regulation and Function of Phosphatidylinositol 3,5-Bisphosphate

2021 ◽  
Author(s):  
Shannon Cheuk Ying Ho
Keyword(s):  
Membrane Trafficking ◽  
Adaptor Protein ◽  
Cellular Functions ◽  
Lipid Kinase ◽  
Cellular Processes ◽  
Lipid Phosphatase ◽  
Tooth Type ◽  
And Function ◽  
Endocytic Compartments ◽  
Lysosomal Acidification

PtdIns(3,5)P2 is a low abundance phosphoinositide that is involved in a variety of cellular processes. Most notably, PtdIns(3,5)P2 is known to regulate vacuolar/lysosomal morphology. Deficiency in PtdIns(3,5)P2 results in enlargement of the yeast vacuole and, an extensive vacuolation of the late endocytic compartments in higher eukaryotes (1, 2). In addition, PtdIns(3,5)P2 is also involved in cellular functions including membrane trafficking, autophagy, and vacuolar/lysosomal acidification. However, the current study provided evidence that shows that the vacuole/lysosomes of PtdIns(3,5)P2-deficient cells remain acidic. Hence, PtdIns(3,5)P2 may not have a role in steady-state vacuolar/lysosomal acidification. PtdIns(3,5)P2 is synthesized by the Fab1 lipid kinase and degraded by the antagonistic Fig4 lipid phosphatase. Vac14, an adaptor protein, is known to interact with both Fab1 and Fig4 to form a complex on the vacuolar membrane. This study demonstrated that Vac14 is required to form a homodimer for its interaction with Fig4 and Fab1. In addition, formation of the homodimer is necessary for regulation of PtdIns(3,5)P2. Mutations in human Vac14 and Fig4 has been identified in patients with neurodegenerative diseases, such as amyotrophic lateral sclerosis and Charcot-Marie-Tooth Type 4J (3, 4). This study provides an important stepping stone in characterizing the regulatory mechanism and understanding the function of PtdIns(3,5)P2

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