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 Nuclear Organization in Stress and Aging

Cells ◽  
2019 ◽  
Vol 8 (7) ◽  
pp. 664 ◽  
Author(s):  
Romero-Bueno ◽  
de la Cruz Ruiz ◽  
Artal-Sanz ◽  
Askjaer ◽  
Dobrzynska
Keyword(s):  
Gene Expression ◽  
Nuclear Envelope ◽  
Nuclear Organization ◽  
3 Dimensional ◽  
Cellular Processes ◽  
Nuclear Lamins ◽  
Nuclear Composition ◽  
Histone Modifiers ◽  
And Function ◽  
Gene Expression Alterations

The eukaryotic nucleus controls most cellular processes. It is isolated from the cytoplasm by the nuclear envelope, which plays a prominent role in the structural organization of the cell, including nucleocytoplasmic communication, chromatin positioning, and gene expression. Alterations in nuclear composition and function are eminently pronounced upon stress and during premature and physiological aging. These alterations are often accompanied by epigenetic changes in histone modifications. We review, here, the role of nuclear envelope proteins and histone modifiers in the 3-dimensional organization of the genome and the implications for gene expression. In particular, we focus on the nuclear lamins and the chromatin-associated protein BAF, which are linked to Hutchinson–Gilford and Nestor–Guillermo progeria syndromes, respectively. We also discuss alterations in nuclear organization and the epigenetic landscapes during normal aging and various stress conditions, ranging from yeast to humans.

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 Structural and Functional Specialization of OSBP-Related Proteins

Contact ◽  
2020 ◽  
Vol 3 ◽  
pp. 251525642094662
Author(s):  
Vanessa Delfosse ◽  
William Bourguet ◽  
Guillaume Drin
Keyword(s):  
Structural Features ◽  
Eukaryotic Cell ◽  
Molecular Architecture ◽  
Lipid Transfer ◽  
Cellular Functions ◽  
Membrane Contact Sites ◽  
Close Proximity ◽  
Tightly Coupled ◽  
And Function ◽  
Related Proteins

Lipids are precisely distributed in the eukaryotic cell where they help to define organelle identity and function, in addition to their structural role. Once synthesized, many lipids must be delivered to other compartments by non-vesicular routes, a process that is undertaken by proteins called Lipid Transfer Proteins (LTPs). OSBP and the closely-related ORP and Osh proteins constitute a major, evolutionarily conserved family of LTPs in eukaryotes. Most of these target one or more subcellular regions, and membrane contact sites in particular, where two organelle membranes are in close proximity. It was initially thought that such proteins were strictly dedicated to sterol sensing or transport. However, over the last decade, numerous studies have revealed that these proteins have many more functions, and we have expanded our understanding of their mechanisms. In particular, many of them are lipid exchangers that exploit PI(4)P or possibly other phosphoinositide gradients to directionally transfer sterol or PS between two compartments. Importantly, these transfer activities are tightly coupled to processes such as lipid metabolism, cellular signalling and vesicular trafficking. This review describes the molecular architecture of OSBP/ORP/Osh proteins, showing how their specific structural features and internal configurations impart unique cellular functions.

scholarly journals Stiffening and inelastic fluidization in vimentin intermediate filament networks

Soft Matter ◽  
2019 ◽  
Vol 15 (36) ◽  
pp. 7127-7136 ◽  
Author(s):  
Anders Aufderhorst-Roberts ◽  
Gijsje H. Koenderink
Keyword(s):  
Intermediate Filaments ◽  
Intermediate Filament ◽  
Shear Rheology ◽  
Cellular Processes ◽  
Filament Networks ◽  
Nonlinear Shear ◽  
Vimentin Intermediate Filament

Nonlinear shear rheology reveals that intermediate filaments balance two contradictory roles: mechanoprotection by stiffening and dynamic cellular processes through softening.

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 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.

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 Eukaryo: An AR and VR Application for Cell Biology

2016 ◽  
Vol 16 (1) ◽  
pp. 7-14
Author(s):  
Douglas Yuen ◽  
Markus Santoso ◽  
Stephen Cartwright ◽  
Christian Jacob
Keyword(s):  
Cell Biology ◽  
High Performance ◽  
Large Scale ◽  
Eukaryotic Cell ◽  
Cellular Functions ◽  
3 Dimensional ◽  
Cellular Processes ◽  
Head Mounted Displays ◽  
Biological Environment ◽  
Immersive Visualization

Eukaryo is a simulated bio-molecular world that allows users to explore the complex environment within a biological cell. Eukaryo was developed using Unity, leveraging the capabilities and high performance of a commercial game engine. Through the use of MiddleVR, our tool can support a wide variety of interaction platforms including 3D virtual reality (VR) environments, such as head-mounted displays, augmented reality (AR) headsets, and large scale immersive visualization facilities. Our interactive, 3-dimensional model demonstrates key functional elements of a generic eukaryotic cell. Users are able to use multiple modes to explore the cell, its structural elements, its organelles, and some key metabolic processes. In contrast to textbook diagrams and even videos, Eukaryo immerses users directly in the biological environment, giving a more effective demonstration of how cellular processes work, how compartmentalization affects cellular functions, and how the machineries of life operate.

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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