scholarly journals Geometric coupling of helicoidal ramps and curvature-inducing proteins in organelle membranes

2019 ◽  
Author(s):  
Morgan Chabanon ◽  
Padmini Rangamani
Keyword(s):  
Minimal Surfaces ◽  
Complex Geometries ◽  
Spontaneous Curvature ◽  
Membrane Structures ◽  
Cellular Functions ◽  
Diverse Range ◽  
Elastic Membranes ◽  
Membrane Geometry ◽  
Membrane Bound ◽  
Shape Equation

AbstractCellular membranes display an incredibly diverse range of shapes, both in the plasma membrane and at membrane bound organelles. These morphologies are intricately related to cellular functions, enabling and regulating fundamental membrane processes. However, the biophysical mechanisms at the origin of these complex geometries are not fully understood from the standpoint of membrane-protein coupling. In this work, we focused on a minimal model of helicoidal ramps representative of specialized endoplasmic reticulum compartments. Given a helicoidal membrane geometry, we asked what is the distribution of spontaneous curvature required to maintain this shape at mechanical equilibrium? Based on the Helfrich energy of elastic membranes with spontaneous curvature, we derived the shape equation for minimal surfaces, and applied it to helicoids. We showed the existence of switches in the sign of the spontaneous curvature associated with geometric variations of the membrane structures. Furthermore, for a prescribed gradient of spontaneous curvature along the exterior boundaries, we identified configurations of the helicoidal ramps that are confined between two infinitely large energy barriers. Overall our results suggest possible mechanisms for geometric control of helicoidal ramps in membrane organelles based on curvature-inducing proteins.

scholarly journals Geometric coupling of helicoidal ramps and curvature-inducing proteins in organelle membranes

2019 ◽  
Vol 16 (158) ◽  
pp. 20190354 ◽  
Author(s):  
Morgan Chabanon ◽  
Padmini Rangamani
Keyword(s):  
Minimal Surfaces ◽  
Complex Geometries ◽  
Spontaneous Curvature ◽  
Membrane Structures ◽  
Cellular Functions ◽  
Diverse Range ◽  
Elastic Membranes ◽  
Membrane Geometry ◽  
Membrane Bound ◽  
Shape Equation

Cellular membranes display an incredibly diverse range of shapes, both in the plasma membrane and at membrane bound organelles. These morphologies are intricately related to cellular functions, enabling and regulating fundamental membrane processes. However, the biophysical mechanisms at the origin of these complex geometries are not fully understood from the standpoint of membrane–protein coupling. In this study, we focused on a minimal model of helicoidal ramps representative of specialized endoplasmic reticulum compartments. Given a helicoidal membrane geometry, we asked what is the distribution of spontaneous curvature required to maintain this shape at mechanical equilibrium? Based on the Helfrich energy of elastic membranes with spontaneous curvature, we derived the shape equation for minimal surfaces, and applied it to helicoids. We showed the existence of switches in the sign of the spontaneous curvature associated with geometric variations of the membrane structures. Furthermore, for a prescribed gradient of spontaneous curvature along the exterior boundaries, we identified configurations of the helicoidal ramps that are confined between two infinitely large energy barriers. Overall our results suggest possible mechanisms for geometric control of helicoidal ramps in membrane organelles based on curvature-inducing proteins.

Clathrin: the molecular shape shifter

2021 ◽  
Vol 478 (16) ◽  
pp. 3099-3123
Author(s):  
Katherine M. Wood ◽  
Corinne J. Smith
Keyword(s):  
Cell Migration ◽  
Molecular Shape ◽  
Coated Vesicle ◽  
Vesicle Formation ◽  
Lattice Structures ◽  
Tubular Structures ◽  
Cellular Functions ◽  
Diverse Range ◽  
Cellular Processes ◽  
Vesicle Recycling

Clathrin is best known for its contribution to clathrin-mediated endocytosis yet it also participates to a diverse range of cellular functions. Key to this is clathrin's ability to assemble into polyhedral lattices that include curved football or basket shapes, flat lattices or even tubular structures. In this review, we discuss clathrin structure and coated vesicle formation, how clathrin is utilised within different cellular processes including synaptic vesicle recycling, hormone desensitisation, spermiogenesis, cell migration and mitosis, and how clathrin's remarkable ‘shapeshifting’ ability to form diverse lattice structures might contribute to its multiple cellular functions.

scholarly journals Cell Secretion: Current Structural and Biochemical Insights

2010 ◽  
Vol 10 ◽  
pp. 2054-2069 ◽  
Author(s):  
Saurabh Trikha ◽  
Elizabeth C. Lee ◽  
Aleksandar M. Jeremic
Keyword(s):  
Plasma Membrane ◽  
Secretory Vesicles ◽  
Intercellular Signaling ◽  
Cell Secretion ◽  
Membrane Structures ◽  
Calcium Dependent ◽  
Cell Plasma ◽  
Membrane Bound ◽  
And Control ◽  
Fusion Pores

Essential physiological functions in eukaryotic cells, such as release of hormones and digestive enzymes, neurotransmission, and intercellular signaling, are all achieved by cell secretion. In regulated (calcium-dependent) secretion, membrane-bound secretory vesicles dock and transiently fuse with specialized, permanent, plasma membrane structures, called porosomes or fusion pores. Porosomes are supramolecular, cup-shaped lipoprotein structures at the cell plasma membrane that mediate and control the release of vesicle cargo to the outside of the cell. The sizes of porosomes range from 150nm in diameter in acinar cells of the exocrine pancreas to 12nm in neurons. In recent years, significant progress has been made in our understanding of the porosome and the cellular activities required for cell secretion, such as membrane fusion and swelling of secretory vesicles. The discovery of the porosome complex and the molecular mechanism of cell secretion are summarized in this article.

scholarly journals Tiny Actors in the Big Cellular World: Extracellular Vesicles Playing Critical Roles in Cancer

2020 ◽  
Vol 21 (20) ◽  
pp. 7688 ◽  
Author(s):  
Ancuta Jurj ◽  
Cecilia Pop-Bica ◽  
Ondrej Slaby ◽  
Cristina D. Ştefan ◽  
William C. Cho ◽  
...  
Keyword(s):  
Extracellular Vesicles ◽  
Molecular Mechanisms ◽  
Recipient Cell ◽  
Cell Communication ◽  
Therapeutic Agents ◽  
Bioactive Molecules ◽  
Cellular Functions ◽  
Membrane Bound

Communications among cells can be achieved either via direct interactions or via secretion of soluble factors. The emergence of extracellular vesicles (EVs) as entities that play key roles in cell-to-cell communication offer opportunities in exploring their features for use in therapeutics; i.e., management and treatment of various pathologies, such as those used for cancer. The potential use of EVs as therapeutic agents is attributed not only for their cell membrane-bound components, but also for their cargos, mostly bioactive molecules, wherein the former regulate interactions with a recipient cell while the latter trigger cellular functions/molecular mechanisms of a recipient cell. In this article, we highlight the involvement of EVs in hallmarks of a cancer cell, particularly focusing on those molecular processes that are influenced by EV cargos. Moreover, we explored the roles of RNA species and proteins carried by EVs in eliciting drug resistance phenotypes. Interestingly, engineered EVs have been investigated and proposed as therapeutic agents in various in vivo and in vitro studies, as well as in several clinical trials.

Inositol pyrophosphates: between signalling and metabolism

2013 ◽  
Vol 452 (3) ◽  
pp. 369-379 ◽  
Author(s):  
Miranda S. C. Wilson ◽  
Thomas M. Livermore ◽  
Adolfo Saiardi
Keyword(s):  
High Energy ◽  
Present Review ◽  
Cellular Functions ◽  
Yeast Saccharomyces Cerevisiae ◽  
Diverse Range ◽  
Inositol Pyrophosphate ◽  
Atp Production ◽  
Recent Innovation ◽  
The Social ◽  
Inositol Pyrophosphates

The present review will explore the insights gained into inositol pyrophosphates in the 20 years since their discovery in 1993. These molecules are defined by the presence of the characteristic ‘high energy’ pyrophosphate moiety and can be found ubiquitously in eukaryotic cells. The enzymes that synthesize them are similarly well distributed and can be found encoded in any eukaryote genome. Rapid progress has been made in characterizing inositol pyrophosphate metabolism and they have been linked to a surprisingly diverse range of cellular functions. Two decades of work is now beginning to present a view of inositol pyrophosphates as fundamental, conserved and highly important agents in the regulation of cellular homoeostasis. In particular it is emerging that energy metabolism, and thus ATP production, is closely regulated by these molecules. Much of the early work on these molecules was performed in the yeast Saccharomyces cerevisiae and the social amoeba Dictyostelium discoideum, but the development of mouse knockouts for IP6K1 and IP6K2 [IP6K is IP6 (inositol hexakisphosphate) kinase] in the last 5 years has provided very welcome tools to better understand the physiological roles of inositol pyrophosphates. Another recent innovation has been the use of gel electrophoresis to detect and purify inositol pyrophosphates. Despite the advances that have been made, many aspects of inositol pyrophosphate biology remain far from clear. By evaluating the literature, the present review hopes to promote further research in this absorbing area of biology.

Outside or inside: role of the subcellular localization of DP4-like enzymes for substrate conversion and inhibitor effects

2011 ◽  
Vol 392 (3) ◽  
Author(s):  
Ute Bank ◽  
Anke Heimburg ◽  
Astrid Wohlfarth ◽  
Gudrun Koch ◽  
Karsten Nordhoff ◽  
...  
Keyword(s):  
Plasma Membrane ◽  
Low Molecular Weight ◽  
Immune Functions ◽  
Cellular Functions ◽  
Fluorogenic Substrates ◽  
Cellular Effects ◽  
Viable Cells ◽  
Substrate Conversion ◽  
Membrane Bound

Abstract The discovery of the DP4-related enzymes DP8 and DP9 raised controversial discussion regarding the physiological and pathophysiological function of distinct members of the DP4 family. Particularly with regard to their potential relevance in regulating immune functions, it is of interest to know which role the subcellular distribution of the enzymes play. Synthetic substrates as well as low molecular weight inhibitors are widely used as tools, but little is yet known regarding their features in cell experiments, such as their plasma membrane penetration capacity. The fluorogenic substrates Gly-Pro-AMC or (Ala-Pro)2-R110 predominantly detect plasma membrane-bound activities of viable cells (less than 0.1% of fluorochromes R110 or AMC inside viable cells after 1 h incubation). Additionally, the selective and non-selective DP8/9 inhibitors allo-Ile-isoindoline and Lys[Z(NO2)]-pyrrolidide were found to be incapable of passing the plasma membrane easily. This suggests that previously reported cellular effects are not due to inhibition of the cytosolic enzymes DP8 or DP9. Moreover, our enzymatic studies with viable cells provided evidence that DP8 and/or DP9 are also present on the surface of immune cells under certain circumstances and could gain relevance particularly in the absence of DP4 expression. In summary, in cells which do express DP4 on the surface, this archetypical member of the DP4 family is the most relevant peptidase in the regulation of cellular functions.

scholarly journals Intracellular wetting mediates contacts between liquid compartments and membrane-bound organelles

2021 ◽  
Vol 220 (10) ◽  
Author(s):  
Halim Kusumaatmaja ◽  
Alexander I. May ◽  
Roland L. Knorr
Keyword(s):  
Phase Separation ◽  
Membrane Interactions ◽  
Cellular Functions ◽  
P Bodies ◽  
Intracellular Degradation ◽  
Wetting Phenomena ◽  
Membrane Bound ◽  
Membrane Contact ◽  
As Stress ◽  
Protein Rich

Protein-rich droplets, such as stress granules, P-bodies, and the nucleolus, perform diverse and specialized cellular functions. Recent evidence has shown the droplets, which are also known as biomolecular condensates or membrane-less compartments, form by phase separation. Many droplets also contact membrane-bound organelles, thereby functioning in development, intracellular degradation, and organization. These underappreciated interactions have major implications for our fundamental understanding of cells. Starting with a brief introduction to wetting phenomena, we summarize recent progress in the emerging field of droplet–membrane contact. We describe the physical mechanism of droplet–membrane interactions, discuss how these interactions remodel droplets and membranes, and introduce "membrane scaffolding" by liquids as a novel reshaping mechanism, thereby demonstrating that droplet–membrane interactions are elastic wetting phenomena. “Membrane-less” and “membrane-bound” condensates likely represent distinct wetting states that together link phase separation with mechanosensitivity and explain key structures observed during embryogenesis, during autophagy, and at synapses. We therefore contend that droplet wetting on membranes provides a robust and intricate means of intracellular organization.

scholarly journals PyInteraph2 and PyInKnife2 to analyze networks in protein structural ensembles

2020 ◽  
Author(s):  
Valentina Sora ◽  
Matteo Tiberti ◽  
Shahriyar Mahdi Robbani ◽  
Joshua Rubin ◽  
Elena Papaleo
Keyword(s):  
Network Models ◽  
Version Control ◽  
Complex Nature ◽  
Cellular Functions ◽  
Diverse Range ◽  
Link Type ◽  
Network Properties ◽  
Protein Ensembles ◽  
The Stability ◽  
Definition Of

AbstractMotivationProtein dynamic is essential for cellular functions. Due to the complex nature of non-covalent interactions and their long-range effects, the analysis of protein conformations using network theory can be enlightening. Protein Structure Networks (PSNs) rely on different philosophies, and the currently available tools suffer from limitations in terms of input formats, supported network models, and version control. Another issue is the precise definition of cutoffs for the network calculations and the assessment of the stability of the parameters, which ultimately affect the outcome of the analyses.ResultsWe provide two open-source software packages, i.e., PyInteraph2 and PyInKnife2, to implement and analyze PSNs in a harmonized, reproducible, and documented manner. PyInteraph2 interfaces with multiple formats for protein ensembles and calculates a diverse range of network models with the possibility to integrate them into a macro-network and perform further downstream graph analyses. PyInKnife2 is a standalone package that supports the network models implemented in PyInteraph2. It employs a jackknife resampling approach to estimate the convergence of network properties and streamline the selection of distance cutoffs. Several functionalities are based on MDAnalysis and NetworkX, including parallelization, and are available for Python 3.7. PyInteraph2 underwent a massive restructuring in terms of setup, installation, and test support compared to the original PyInteraph software.ConclusionsWe foresee that the modular structure of the code and the version control system of GitHub will promote the transition to a community-driven effort, boost reproducibility, and establish harmonized protocols in the PSN field. As developers, we will guarantee the introduction of new functionalities, assistance, training of new contributors, and maintenance of the package.AvailabilityThe packages are available at https://github.com/ELELAB/pyinteraph2 and https://github.com/ELELAB/PyInKnife2 with guides provided within the packages.

scholarly journals Broken detailed balance and entropy production in the human brain

2021 ◽  
Vol 118 (47) ◽  
pp. e2109889118
Author(s):  
Christopher W. Lynn ◽  
Eli J. Cornblath ◽  
Lia Papadopoulos ◽  
Maxwell A. Bertolero ◽  
Danielle S. Bassett
Keyword(s):  
Human Brain ◽  
Entropy Production ◽  
Large Scale ◽  
Detailed Balance ◽  
Neural Systems ◽  
Imaging Data ◽  
Cellular Functions ◽  
Diverse Range ◽  
Brain Imaging Data ◽  
Dynamic Ising Model

Living systems break detailed balance at small scales, consuming energy and producing entropy in the environment to perform molecular and cellular functions. However, it remains unclear how broken detailed balance manifests at macroscopic scales and how such dynamics support higher-order biological functions. Here we present a framework to quantify broken detailed balance by measuring entropy production in macroscopic systems. We apply our method to the human brain, an organ whose immense metabolic consumption drives a diverse range of cognitive functions. Using whole-brain imaging data, we demonstrate that the brain nearly obeys detailed balance when at rest, but strongly breaks detailed balance when performing physically and cognitively demanding tasks. Using a dynamic Ising model, we show that these large-scale violations of detailed balance can emerge from fine-scale asymmetries in the interactions between elements, a known feature of neural systems. Together, these results suggest that violations of detailed balance are vital for cognition and provide a general tool for quantifying entropy production in macroscopic systems.

scholarly journals The Membrane Associated RING-CH Proteins: A Family of E3 Ligases with Diverse Roles through the Cell

2014 ◽  
Vol 2014 ◽  
pp. 1-23 ◽  
Author(s):  
Tasleem Samji ◽  
Soonwook Hong ◽  
Robert E. Means
Keyword(s):  
Signal Transduction ◽  
Dna Repair ◽  
Essential Role ◽  
Proteolytic Degradation ◽  
Diverse Range ◽  
E3 Ligases ◽  
Cellular Processes ◽  
Range Of Functions ◽  
Membrane Bound ◽  
Lines Of Evidence

Since the discovery that conjugation of ubiquitin to proteins can drive proteolytic degradation, ubiquitination has been shown to perform a diverse range of functions in the cell. It plays an important role in endocytosis, signal transduction, trafficking of vesicles inside the cell, and even DNA repair. The process of ubiquitination-mediated control has turned out to be remarkably complex, involving a diverse array of proteins and many levels of control. This review focuses on a family of structurally related E3 ligases termed the membrane-associated RING-CH (MARCH) ubiquitin ligases, which were originally discovered as structural homologs to the virals E3s, K3, and K5 from Kaposi’s sarcoma-associated herpesvirus (KSHV). These proteins contain a catalytic RING-CH finger and are typically membrane-bound, with some having up to 14 putative transmembrane domains. Despite several lines of evidence showing that the MARCH proteins play a complex and essential role in several cellular processes, this family remains understudied.

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