scholarly journals Defects in Structural Integrity of Ergosterol and the Cdc50p-Drs2p Putative Phospholipid Translocase Cause Accumulation of Endocytic Membranes, onto Which Actin Patches Are Assembled in Yeast

2005 ◽  
Vol 16 (12) ◽  
pp. 5592-5609 ◽  
Author(s):  
Takuma Kishimoto ◽  
Takaharu Yamamoto ◽  
Kazuma Tanaka

Specific changes in membrane lipid composition are implicated in actin cytoskeletal organization, vesicle formation, and control of cell polarity. Cdc50p, a membrane protein in the endosomal/trans-Golgi network compartments, is a noncatalytic subunit of Drs2p, which is implicated in translocation of phospholipids across lipid bilayers. We found that the cdc50Δ mutation is synthetically lethal with mutations affecting the late steps of ergosterol synthesis (erg2 to erg6). Defects in cell polarity and actin organization were observed in the cdc50Δ erg3Δ mutant. In particular, actin patches, which are normally found at cortical sites, were assembled intracellularly along with their assembly factors, including Las17p, Abp1p, and Sla2p. The exocytic SNARE Snc1p, which is recycled by an endocytic route, was also intracellularly accumulated, and inhibition of endocytic internalization suppressed the cytoplasmic accumulation of both Las17p and Snc1p. Simultaneous loss of both phospholipid asymmetry and sterol structural integrity could lead to accumulation of endocytic intermediates capable of initiating assembly of actin patches in the cytoplasm.

2017 ◽  
Author(s):  
Melina J. Scholze ◽  
Kévin S. Barbieux ◽  
Alessandro De Simone ◽  
Mathilde Boumasmoud ◽  
Camille C. N. Süess ◽  
...  

AbstractAsymmetric division is crucial for embryonic development and stem cell lineages. In the one-cellC. elegansembryo, a contractile cortical actomyosin network contributes to anterior-posterior (A-P) polarity and asymmetric division by segregating PAR proteins to discrete cortical domains. Here, we discovered that the plasma membrane lipid phosphatidylinositol 4,5-bisphosphate (PIP2) forms dynamic structures inC. eleganszygotes, distributing in a polarized and PAR-dependent manner along the A-P axis. PIP2cortical structures overlap with F-actin and coincide with the actin regulators RHO-1, CDC-42 and ECT-2. Particle image velocimetry analysis revealed that PIP2and F-actin cortical movements are coupled, with PIP2structures moving slightly ahead. Importantly, we established that PIP2cortical structures form in an actin-dependent manner and, conversely, that decreasing or increasing the level of PIP2results in severe F-actin disorganization, revealing the interdependence between these components. Furthermore, we uncovered that PIP2regulates the sizing of PAR cortical domains. Overall, our work establishes for the first time that a lipid membrane component, PIP2, is a critical modulator of actin organization and cell polarity inC. elegansembryos.Summary statementPI(4,5)P2is distributed in dynamic cortical structures and regulates asymmetric division by controlling actin organization and cell polarity in the one-cellC. elegansembryo.


Membranes ◽  
2021 ◽  
Vol 11 (8) ◽  
pp. 562
Author(s):  
Miliça Ristovski ◽  
Danny Farhat ◽  
Shelly Ellaine M. Bancud ◽  
Jyh-Yeuan Lee

Lipid composition in cellular membranes plays an important role in maintaining the structural integrity of cells and in regulating cellular signaling that controls functions of both membrane-anchored and cytoplasmic proteins. ATP-dependent ABC and P4-ATPase lipid transporters, two integral membrane proteins, are known to contribute to lipid translocation across the lipid bilayers on the cellular membranes. In this review, we will highlight current knowledge about the role of cholesterol and phospholipids of cellular membranes in regulating cell signaling and how lipid transporters participate this process.


Cells ◽  
2021 ◽  
Vol 10 (7) ◽  
pp. 1618
Author(s):  
Yuichi Wakana ◽  
Felix Campelo

Membrane trafficking is essential for processing and transport of proteins and lipids and to establish cell compartmentation and tissue organization. Cells respond to their needs and control the quantity and quality of protein secretion accordingly. In this review, we focus on a particular membrane trafficking route from the trans-Golgi network (TGN) to the cell surface: protein kinase D (PKD)-dependent pathway for constitutive secretion mediated by carriers of the TGN to the cell surface (CARTS). Recent findings highlight the importance of lipid signaling by organelle membrane contact sites (MCSs) in this pathway. Finally, we discuss our current understanding of multiple signaling pathways for membrane trafficking regulation mediated by PKD, G protein-coupled receptors (GPCRs), growth factors, metabolites, and mechanosensors.


Author(s):  
Torgeir Moan

Based on relevant accident experiences with oil and gas platforms, a brief overview of structural integrity management of offshore structures is given; including an account of adequate design criteria, inspection, repair and maintenance as well as quality assurance and control of the engineering processes. The focus is on developing research based design standards for Accidental Collapse Limit States to ensure robustness or damage tolerance in view damage caused by accidental loads due to operational errors and to some extent abnormal structural damage due to fabrication errors. Moreover, it is suggested to provide robustness in cases where the structural performance is sensitive to uncertain parameters. The use of risk assessment to aid decisions in lieu of uncertainties affecting the performance of novel and existing offshore structures, is briefly addressed.


Antioxidants ◽  
2020 ◽  
Vol 9 (5) ◽  
pp. 430 ◽  
Author(s):  
Anja Sadžak ◽  
Janez Mravljak ◽  
Nadica Maltar-Strmečki ◽  
Zoran Arsov ◽  
Goran Baranović ◽  
...  

The structural integrity, elasticity, and fluidity of lipid membranes are critical for cellular activities such as communication between cells, exocytosis, and endocytosis. Unsaturated lipids, the main components of biological membranes, are particularly susceptible to the oxidative attack of reactive oxygen species. The peroxidation of unsaturated lipids, in our case 1,2-dioleoyl-sn-glycero-3-phosphocholine (DOPC), induces the structural reorganization of the membrane. We have employed a multi-technique approach to analyze typical properties of lipid bilayers, i.e., roughness, thickness, elasticity, and fluidity. We compared the alteration of the membrane properties upon initiated lipid peroxidation and examined the ability of flavonols, namely quercetin (QUE), myricetin (MCE), and myricitrin (MCI) at different molar fractions, to inhibit this change. Using Mass Spectrometry (MS) and Fourier Transform Infrared Spectroscopy (FTIR), we identified various carbonyl products and examined the extent of the reaction. From Atomic Force Microscopy (AFM), Force Spectroscopy (FS), Small Angle X-Ray Scattering (SAXS), and Electron Paramagnetic Resonance (EPR) experiments, we concluded that the membranes with inserted flavonols exhibit resistance against the structural changes induced by the oxidative attack, which is a finding with multiple biological implications. Our approach reveals the interplay between the flavonol molecular structure and the crucial membrane properties under oxidative attack and provides insight into the pathophysiology of cellular oxidative injury.


2018 ◽  
Vol 315 (4) ◽  
pp. R656-R667 ◽  
Author(s):  
Wen Yu Wong ◽  
Maricela Pier ◽  
Kirsten H. Limesand

Xerostomia and hyposalivation are debilitating side effects for patients treated with ionizing radiation for head and neck cancer. Despite technological advances, collateral damage to the salivary glands remains a significant problem for patients and severely diminishes their quality of life. During the wound healing process, restoration of junctional contacts is necessary to maintain polarity, structural integrity, and orientation cues for secretion. However, little is known about whether these structural molecules are impacted following radiation damage and more importantly, during tissue restoration. We evaluated changes in adherens junctions and cytoskeletal regulators in an injury model where mice were irradiated with 5 Gy and a restoration model where mice injected postradiation with insulin-like growth factor 1 (IGF1) are capable of restoring salivary function. Using coimmunoprecipitation, there is a decrease in epithelial (E)-cadherin bound to β-catenin following damage that is restored to untreated levels with IGF1. Via its adaptor proteins, β-catenin links the cadherins to the cytoskeleton and part of this regulation is mediated through Rho-associated coiled-coil containing kinase (ROCK) signaling. In our radiation model, filamentous (F)-actin organization is fragmented, and there is an induction of ROCK activity. However, a ROCK inhibitor, Y-27632, prevents E-cadherin/β-catenin dissociation following radiation treatment. These findings illustrate that radiation induces a ROCK-dependent disruption of the cadherin-catenin complex and alters F-actin organization at stages of damage when hyposalivation is observed. Understanding the regulation of these components will be critical in the discovery of therapeutics that have the potential to restore function in polarized epithelium.


Statistical variations in input parameters that affect structural reliability have historically been incorporated approximately in engineering designs by application of safety factors. Increased concerns over the injury potential and costs of licensing, insurance, field repairs or recalls, and product liability claims now demand more quantitative evaluation of possible flaws or unusual usage conditions that might result from statistical variations or uncertainties. This paper describes the basic concepts of probabilistic fracture mechanics that are used to assess and control risk. Recent developments in combined analysis methods are presented that utilize field experience data with probabilistic analysis to improve the accuracy of the structural integrity predictions. Several specific examples are described that illustrate how these probabilistic methods are used to assess risk and to provide a quantitative basis for establishing design, operation or maintenance allowables. These procedures, which realistically model the actual statistical variations that exist, can eliminate unnecessarily conservative approximations and often achieve improved reliability at reduced cost.


Polymers ◽  
2019 ◽  
Vol 11 (5) ◽  
pp. 891 ◽  
Author(s):  
Alessandro Angelin ◽  
Uwe Bog ◽  
Ravi Kumar ◽  
Christof M. Niemeyer ◽  
Michael Hirtz

Lipid-based membranes play crucial roles in regulating the interface between cells and their external environment, the communication within cells, and cellular sensing. To study these important processes, various lipid-based artificial membrane models have been developed in recent years and, indeed, large-area arrays of supported lipid bilayers suit the needs of many of these studies remarkably well. Here, the direct-write scanning probe lithography technique called polymer pen lithography (PPL) was used as a tool for the creation of lipid micropatterns over large areas via polymer-stamp-mediated transfer of lipid-containing inks onto glass substrates. In order to better understand and control the lipid transfer in PPL, we conducted a systematic study of the influence of dwell time (i.e., duration of contact between tip and sample), humidity, and printing pressure on the outcome of PPL with phospholipids and discuss results in comparison to the more often studied dip-pen nanolithography with phospholipids. This is the first systematic study in phospholipid printing with PPL. Biocompatibility of the obtained substrates with up to two different ink compositions was demonstrated. The patterns are suitable to serve as a platform for mast cell activation experiments.


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