DHCR24 Knockdown Lead to Hyperphosphorylation of Tau at Thr181, Thr231, Ser262, Ser396, and Ser422 Sites by Membrane Lipid-Raft Dependent PP2A Signaling in SH-SY5Y Cells

2021 ◽  
Author(s):  
Zihan Qi ◽  
Ying Zhang ◽  
Kai Yao ◽  
Mengqi Zhang ◽  
Yixuan Xu ◽  
...  
Keyword(s):  
Lipid Raft ◽  
Membrane Lipid

scholarly journals A New Membrane Lipid Raft Gene SpFLT-1 Facilitating the Endocytosis of Vibrio alginolyticus in the Crab Scylla paramamosain

PLoS ONE ◽  
2015 ◽  
Vol 10 (7) ◽  
pp. e0133443 ◽  
Author(s):  
Fangyi Chen ◽  
Jun Bo ◽  
Xiaowan Ma ◽  
Lixia Dong ◽  
Zhongguo Shan ◽  
...  
Keyword(s):  
Lipid Raft ◽  
Membrane Lipid ◽  
Vibrio Alginolyticus ◽  
Scylla Paramamosain

scholarly journals Interaction of drugs with lipid raft membrane domains as a possible target

2020 ◽  
Vol 14 (1) ◽  
pp. 34-47
Author(s):  
Hironori Tsuchiya ◽  
Maki Mizogami
Keyword(s):  
Membrane Fluidity ◽  
Lipid Rafts ◽  
Lipid Raft ◽  
Plasma Membranes ◽  
Cellular Membrane ◽  
Membrane Lipid ◽  
Membrane Domains ◽  
Functional Protein ◽  
Lipid Complex ◽  
Physicochemical Changes

Introduction: Plasma membranes are not the homogeneous bilayers of uniformly distributed lipids but the lipid complex with laterally separated lipid raft membrane domains, which provide receptor, ion channel and enzyme proteins with a platform. The aim of this article is to review the mechanistic interaction of drugs with membrane lipid rafts and address the question whether drugs induce physicochemical changes in raft-constituting and raft-surrounding membranes. Methods: Literature searches of PubMed/MEDLINE and Google Scholar databases from 2000 to 2020 were conducted to include articles published in English in internationally recognized journals. Collected articles were independently reviewed by title, abstract and text for relevance. Results: The literature search indicated that pharmacologically diverse drugs interact with raft model membranes and cellular membrane lipid rafts. They could physicochemically modify functional protein-localizing membrane lipid rafts and the membranes surrounding such domains, affecting the raft organizational integrity with the resultant exhibition of pharmacological activity. Raft-acting drugs were characterized as ones to decrease membrane fluidity, induce liquid-ordered phase or order plasma membranes, leading to lipid raft formation; and ones to increase membrane fluidity, induce liquid-disordered phase or reduce phase transition temperature, leading to lipid raft disruption. Conclusion: Targeting lipid raft membrane domains would open a new way for drug design and development. Since angiotensin-converting enzyme 2 receptors which are a cell-specific target of and responsible for the cellular entry of novel coronavirus are localized in lipid rafts, agents that specifically disrupt the relevant rafts may be a drug against coronavirus disease 2019.

scholarly journals Moderate Static Magnetic Field (6 mT)-Induced Lipid Rafts Rearrangement Increases Silver NPs Uptake in Human Lymphocytes

Molecules ◽  
2020 ◽  
Vol 25 (6) ◽  
pp. 1398
Author(s):  
Cristian Vergallo ◽  
Elisa Panzarini ◽  
Bernardetta Anna Tenuzzo ◽  
Stefania Mariano ◽  
Ada Maria Tata ◽  
...  
Keyword(s):  
Plasma Membrane ◽  
Lipid Rafts ◽  
Lipid Raft ◽  
Human Lymphocytes ◽  
Peripheral Blood Lymphocytes ◽  
Membrane Lipid ◽  
Membrane Perturbation ◽  
Plasma Membrane Lipid ◽  
Silver Nps ◽  
Surface Ligand

One of the most relevant drawbacks in medicine is the ability of drugs and/or imaging agents to reach cells. Nanotechnology opened new horizons in drug delivery, and silver nanoparticles (AgNPs) represent a promising delivery vehicle for their adjustable size and shape, high-density surface ligand attachment, etc. AgNPs cellular uptake involves different endocytosis mechanisms, including lipid raft-mediated endocytosis. Since static magnetic fields (SMFs) exposure induces plasma membrane perturbation, including the rearrangement of lipid rafts, we investigated whether SMF could increase the amount of AgNPs able to pass the peripheral blood lymphocytes (PBLs) plasma membrane. To this purpose, the effect of 6-mT SMF exposure on the redistribution of two main lipid raft components (i.e., disialoganglioside GD3, cholesterol) and on AgNPs uptake efficiency was investigated. Results showed that 6 mT SMF: (i) induces a time-dependent GD3 and cholesterol redistribution in plasma membrane lipid rafts and modulates gene expression of ATP-binding cassette transporter A1 (ABCA1), (ii) increases reactive oxygen species (ROS) production and lipid peroxidation, (iii) does not induce cell death and (iv) induces lipid rafts rearrangement, that, in turn, favors the uptake of AgNPs. Thus, it derives that SMF exposure could be exploited to enhance the internalization of NPs-loaded therapeutic or diagnostic molecules.

scholarly journals Activation of integrin α5 mediated by flow requires its translocation to membrane lipid rafts in vascular endothelial cells

2016 ◽  
Vol 113 (3) ◽  
pp. 769-774 ◽  
Author(s):  
Xiaoli Sun ◽  
Yi Fu ◽  
Mingxia Gu ◽  
Lu Zhang ◽  
Dan Li ◽  
...  
Keyword(s):  
Endothelial Cells ◽  
Shear Stress ◽  
Lipid Rafts ◽  
Lipid Raft ◽  
Density Lipoprotein ◽  
Membrane Lipid ◽  
Local Flow ◽  
Atherosclerotic Lesions ◽  
Integrin Α5

Local flow patterns determine the uneven distribution of atherosclerotic lesions. Membrane lipid rafts and integrins are crucial for shear stress-regulated endothelial function. In this study, we investigate the role of lipid rafts and integrin α5 in regulating the inflammatory response in endothelial cells (ECs) under atheroprone versus atheroprotective flow. Lipid raft proteins were isolated from ECs exposed to oscillatory shear stress (OS) or pulsatile shear stress, and then analyzed by quantitative proteomics. Among 396 proteins redistributed in lipid rafts, integrin α5 was the most significantly elevated in lipid rafts under OS. In addition, OS increased the level of activated integrin α5 in lipid rafts through the regulation of membrane cholesterol and fluidity. Disruption of F-actin-based cytoskeleton and knockdown of caveolin-1 prevented the OS-induced integrin α5 translocation and activation. In vivo, integrin α5 activation and EC dysfunction were observed in the atheroprone areas of low-density lipoprotein receptor-deficient (Ldlr−/−) mice, and knockdown of integrin α5 markedly attenuated EC dysfunction in partially ligated carotid arteries. Consistent with these findings, mice with haploinsufficency of integrin α5 exhibited a reduction of atherosclerotic lesions in the regions under atheroprone flow. The present study has revealed an integrin- and membrane lipid raft-dependent mechanotransduction mechanism by which atheroprone flow causes endothelial dysfunction.

scholarly journals Salicylic acid-mediated plasmodesmal closure via Remorin-dependent lipid organization

2019 ◽  
Vol 116 (42) ◽  
pp. 21274-21284 ◽  
Author(s):  
Dingquan Huang ◽  
Yanbiao Sun ◽  
Zhiming Ma ◽  
Meiyu Ke ◽  
Yong Cui ◽  
...  
Keyword(s):  
Salicylic Acid ◽  
Lipid Raft ◽  
Plant Pathogens ◽  
Regulatory Protein ◽  
Cell Communication ◽  
Direct Interaction ◽  
Membrane Lipid ◽  
Dependent Manner ◽  
Transmission Electron ◽  
Lipid Organization

Plasmodesmata (PD) are plant-specific membrane-lined channels that create cytoplasmic and membrane continuities between adjacent cells, thereby facilitating cell–cell communication and virus movement. Plant cells have evolved diverse mechanisms to regulate PD plasticity in response to numerous environmental stimuli. In particular, during defense against plant pathogens, the defense hormone, salicylic acid (SA), plays a crucial role in the regulation of PD permeability in a callose-dependent manner. Here, we uncover a mechanism by which plants restrict the spreading of virus and PD cargoes using SA signaling by increasing lipid order and closure of PD. We showed that exogenous SA application triggered the compartmentalization of lipid raft nanodomains through a modulation of the lipid raft-regulatory protein, Remorin (REM). Genetic studies, superresolution imaging, and transmission electron microscopy observation together demonstrated that Arabidopsis REM1.2 and REM1.3 are crucial for plasma membrane nanodomain assembly to control PD aperture and functionality. In addition, we also found that a 14-3-3 epsilon protein modulates REM clustering and membrane nanodomain compartmentalization through its direct interaction with REM proteins. This study unveils a molecular mechanism by which the key plant defense hormone, SA, triggers membrane lipid nanodomain reorganization, thereby regulating PD closure to impede virus spreading.

scholarly journals Membrane lipid rafts are disturbed in the response of rat skeletal muscle to short-term disuse

2017 ◽  
Vol 312 (5) ◽  
pp. C627-C637 ◽  
Author(s):  
Alexey M. Petrov ◽  
Violetta V. Kravtsova ◽  
Vladimir V. Matchkov ◽  
Alexander N. Vasiliev ◽  
Andrey L. Zefirov ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Plasma Membrane ◽  
Lipid Rafts ◽  
Lipid Raft ◽  
Motor Nerve ◽  
Membrane Lipid ◽  
Hindlimb Suspension ◽  
Cholera Toxin B Subunit ◽  
Plasma Membrane Lipid ◽  
Intracellular Ca

Marked loss of skeletal muscle mass occurs under various conditions of disuse, but the molecular and cellular mechanisms leading to atrophy are not completely understood. We investigate early molecular events that might play a role in skeletal muscle remodeling during mechanical unloading (disuse). The effects of acute (6–12 h) hindlimb suspension on the soleus muscles from adult rats were examined. The integrity of plasma membrane lipid rafts was tested utilizing cholera toxin B subunit or fluorescent sterols. In addition, resting intracellular Ca2+ level was analyzed. Acute disuse disturbed the plasma membrane lipid-ordered phase throughout the sarcolemma and was more pronounced in junctional membrane regions. Ouabain (1 µM), which specifically inhibits the Na-K-ATPase α2 isozyme in rodent skeletal muscles, produced similar lipid raft changes in control muscles but was ineffective in suspended muscles, which showed an initial loss of α2 Na-K-ATPase activity. Lipid rafts were able to recover with cholesterol supplementation, suggesting that disturbance results from cholesterol loss. Repetitive nerve stimulation also restores lipid rafts, specifically in the junctional sarcolemma region. Disuse locally lowered the resting intracellular Ca2+ concentration only near the neuromuscular junction of muscle fibers. Our results provide evidence to suggest that the ordering of lipid rafts strongly depends on motor nerve input and may involve interactions with the α2 Na-K-ATPase. Lipid raft disturbance, accompanied by intracellular Ca2+ dysregulation, is among the earliest remodeling events induced by skeletal muscle disuse.

scholarly journals Effects of integrin-mediated cell adhesion on plasma membrane lipid raft components and signaling

2011 ◽  
Vol 22 (18) ◽  
pp. 3456-3464 ◽  
Author(s):  
Andrés Norambuena ◽  
Martin A. Schwartz
Keyword(s):  
Plasma Membrane ◽  
Cell Adhesion ◽  
Lipid Raft ◽  
Rho Gtpases ◽  
Cancer Metastasis ◽  
Cyclic Adenosine Monophosphate ◽  
Adenosine Monophosphate ◽  
Membrane Lipid ◽  
Cell Detachment ◽  
Suspended Cells

Anchorage dependence of cell growth, which is mediated by multiple integrin-regulated signaling pathways, is a key defense against cancer metastasis. Detachment of cells from the extracellular matrix triggers caveolin-1–dependent internalization of lipid raft components, which mediates suppression of Rho GTPases, Erk, and phosphatidylinositol 3-kinase in suspended cells. Elevation of cyclic adenosine monophosphate (cAMP) following cell detachment is also implicated in termination of growth signaling in suspended cells. Studies of integrins and lipid rafts, however, examined mainly ganglioside GM1 and glycosylphosphatidylinositol-linked proteins as lipid raft markers. In this study, we examine a wider range of lipid raft components. Whereas many raft components internalized with GM1 following cell detachment, flotillin2, connexin43, and Gαs remained in the plasma membrane. Loss of cell adhesion caused movement of many components from the lipid raft to the nonraft fractions on sucrose gradients, although flotillin2, connexin43, and H-Ras were resistant. Gαs lost its raft association, concomitant with cAMP production. Modification of the lipid tail of Gαs to increase its association with ordered domains blocked the detachment-induced increase in cAMP. These data define the effects of that integrin-mediated adhesion on the localization and behavior of a variety of lipid raft components and reveal the mechanism of the previously described elevation of cAMP after cell detachment.

Membrane Derived Micorvesicles - Underappreciated Components of the Tumor Microenvironment That Modulate Tumor Growth, Vascularization and Metastasis.

Blood ◽  
2005 ◽  
Vol 106 (11) ◽  
pp. 473-473
Author(s):  
Marcin Wysoczynski ◽  
Fadhi Hayek ◽  
Janina Ratajczak ◽  
Anna Janowska-Wieczorek ◽  
Mariusz Z. Ratajczak
Keyword(s):  
Lung Cancer ◽  
Bone Marrow ◽  
Endothelial Cells ◽  
Tumor Microenvironment ◽  
Cell Surface ◽  
Cancer Cells ◽  
Lipid Raft ◽  
Membrane Lipid ◽  
Target Cells

Abstract Viable eukaryotic cells shed circular membrane fragments called microvesicles (MV) from the cell surface and secrete them from the endosomal compartments. These MV, which are different from apoptotic bodies, are enriched in lipids, proteins and mRNA. We postulate that MV play an important and underappreciated role in cell-cell communication by i) stimulating target cells with ligands that the MV express, ii) fusing with target cells and thus transferring various receptors to their surface, and iii) delivering mRNA, lipids and proteins. Since tumor cells secrete large quantities of MV we hypothesized that the latter are important constituents of the tumor microenvironment and their role in tumor progression merited investigation. First, we observed that human and murine lung cancer cell lines secrete more MV in response to non-apoptotic doses of hypoxia, irradiation and chemotherapy. The MV derived from human cancer cells chemoattracted bone marrow-, lymph node- and lung-derived fibroblasts and endothelial cells and activated in these stromal cells the phosphorylation of MAPKp42/44 and AKT. Furthermore, they also induced in bone marrow- and lung-derived fibroblasts expression of LIF, OSM, IL-11, VEGF and MMP-9. Moreover, conditioned media from marrow fibroblasts exposed to MV induced phosphorylation of STAT-3 proteins and chemoattracted lung cancer cells in a LIF- and OSM-dependent manner and, together with IL-11 and VEGF, activated osteoclasts and endothelial cells. Furthermore, MV from cancer cells embedded in Matrigel implants strongly stimulated angiogenesis. We also found that tumor-derived MV express tissue factor (TF) and activate platelets and as a result of this MV derived from activated platelets transfer several adhesion molecules from platelets to the tumor cell surface. This increases adhesiveness of lung cancer cells in endothelium and their metastatic spread in vivo after injection into syngeneic mice. Finally, we found that formation of MV depends on the formation of membrane lipid rafts. Thus we postulate that tumor- and platelet-derived MV are underappreciated constituents of the tumor microenvironment and play a pivotal role in tumor progression/metastasis and angiogenesis. As MV formation appears to be lipid raft-dependent, we suggest that inhibitors of membrane lipid raft formation (e.g, statins or polyene antibiotics) could decrease MV-dependent tumor spread/growth and we are currently testing this hypothesis in animal models in vivo.

scholarly journals Modulation of Purinergic Signaling Prior to Transplantation Both in Hematopoietic Stem Progenitor Cells (HSPCs) or Recipient Bone Marrow (BM) Microenvironment - As Novel Strategies to Accelerate and Facilitate HSPCs Homing and Engraftment

Blood ◽  
2021 ◽  
Vol 138 (Supplement 1) ◽  
pp. 3809-3809
Author(s):  
Mateusz Adamiak ◽  
Arjun Thapa ◽  
Kamila Bujko ◽  
Katarzyna Brzeźniakiewicz-Janus ◽  
Janina Ratajczak ◽  
...  
Keyword(s):  
Progenitor Cells ◽  
Lipid Raft ◽  
Nlrp3 Inflammasome ◽  
Ex Vivo ◽  
Purinergic Signaling ◽  
Membrane Lipid ◽  
Short Exposure ◽  
Heme Oxygenase 1 ◽  
Dependent Manner ◽  
Hematopoietic Stem

Abstract Background. The success rate of hematopoietic stem cell transplantation strongly depends on the number of transplanted hematopoietic stem/progenitor cells (HSPCs) and their speed of engraftment after infusion to the myeloablated transplant recipient. Therefore, clinical outcomes will benefit from accelerating the speed of homing and engraftment rate of transplanted HSPCs. This is important when the number of available HSPCs is low, as seen after poor harvest from BM, poor mobilization efficiency of the donor, and a low number of HSPCs present in the available umbilical cord blood (UCB) unit for an adult recipient. Our recent research demonstrated that purinergic signaling involving extracellular adenosine triphosphate (eATP) and its extracellular metabolite adenosine (eAdo) play a significant opposite role in homing/engraftment of HSPCs - reviewed in Curr Opin Hematol 2021, 28:251-261. To explain this eATP released from the cells of conditioned for transplantation by myeloablation recipient's BM facilitates homing of HSPCs, and subsequently becomes metabolized by cell surface ectonucleotidases CD39 and CD73 to eAdo, that inhibits this process. Therefore, eATP and eAdo upregulated in PB and BM modulate homing/engraftment in i) infused to the recipient donor-derived HSPCs and ii) in recipient BM microenvironment - in an opposite way. We also reported that the beneficial effect of eATP on homing/engraftment of HSPCs depends on the promotion of membrane lipid raft formation on the surface of HSPCs that incorporate homing receptors for their optimal interaction with BM released homing chemoattractants. This process is promoted by eATP activated Nlrp3 inflammasome. On the other hand, Nlrp3 inflammasome and membrane lipid raft formation are inhibited by eAdo in heme oxygenase-1 (HO-1)-dependent manner (Leukemia 2020; 34:1512-1523). Hypothesis. We hypothesized that proper modulation of eATP - eAdo signaling both at the level of transplanted HSPCs and recipient BM microenvironment will speed up the seeding efficiency of transplanted cells to BM niches. Material and Methods. We exposed HSPCs before transplantation ex vivo to i) exogenous eATP or ii) small molecular CD39 and CD73 inhibitors. We also inhibited CD39 and CD73 in transplant recipients BM at the time of myeloablative conditioning. In addition, we also activated ex vivo Nlrp3 inflammasome in HSPCs to be transplanted by specific activator nigericin. In control experiments, eATP stimulated Nlrp3 inflammasome activity was inhibited by the HO-1 activator that is CoPP. Homing of HSPCs was evaluated by measuring a number of donor-derived fluorochrome-labeled cells and clonogenic progenitors in BM of myeloablated hosts at 24 hours after transplantation. Early engraftment was assessed by counting the number of CFU-S and clonogeneic progenitors 12 days after transplantation and by evaluating kinetics of recovery of PB hematopoietic cell counts. Finally, while activation of Nlrp3 inflammasome was assessed by immunofluorescence assay, membrane lipid raft formation was evaluated by confocal microscopy. Results. We noticed that homing and engraftment of HSPCs was significantly accelerated after i) short exposure before transplantation to eATP, ii) inhibition of eAdo formation by CD39, and CD73 inhibitors, and iii) activation of Nlrp3 inflammasome by nigericin. Similarly, inhibition of eAdo formation in recipient BM microenvironment of transplanted mice by CD39 and CD73 inhibitors also improved homing and engraftment efficiency. This correlated with activation in the eATP-dependent manner of Nlrp3 inflammasome in HSPCs followed by membrane lipid raft formation. In the BM microenvironment, upregulation of eATP and inhibition of eAdo also enhanced expression of homing chemoattractants. Conclusions. Since all purinergic signaling modifiers employed in our studies are non-toxic against HSPCs, our data obtained in the animal model indicates that modulation of purinergic signaling before transplantation in HSPCs as well as in BM of the myeloablated recipient would significantly accelerate hematopoietic recovery after hematopoietic transplantation. Disclosures No relevant conflicts of interest to declare.

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