Piercing the lipid raft: the case of Vibrio cholerae cytolysin

2018 ◽  
Vol 475 (24) ◽  
pp. 3917-3919
Author(s):  
Normand Cyr
Keyword(s):  
Vibrio Cholerae ◽  
Lipid Bilayer ◽  
Lipid Raft ◽  
Pore Formation ◽  
Membrane Binding ◽  
Membrane Lipid ◽  
Recent Issue ◽  
Biochemical Journal ◽  
Oligomeric Assembly ◽  
Binding Capability

In a recent issue of Biochemical Journal, Kathuria et al. [Biochem. J. (2018) 475, 3039–3055] report that membrane binding of the pore-forming toxin Vibrio cholerae cytolysin (VCC) is facilitated by the presence of cholesterol, and the presence of this sterol within the lipid bilayer is key for the formation of a functional pore. Yet, in the presence of accessory non-lipid components, VCC retains its membrane-binding capability likely through membrane lipid raft structures. In light of their results, the authors provide new insights into the roles of cholesterol and of membrane microstructures in the binding, the oligomeric assembly and the cytolytic pore formation of VCC which all take place following infection by V. cholerae.

Revisiting the role of cholesterol in regulating the pore-formation mechanism of Vibrio cholerae cytolysin, a membrane-damaging β-barrel pore-forming toxin

2018 ◽  
Vol 475 (19) ◽  
pp. 3039-3055 ◽  
Author(s):  
Reema Kathuria ◽  
Anish Kumar Mondal ◽  
Rohan Sharma ◽  
Samarjit Bhattacharyya ◽  
Kausik Chattopadhyay
Keyword(s):  
Vibrio Cholerae ◽  
Formation Mechanism ◽  
Pore Formation ◽  
Critical Role ◽  
Lipid Vesicles ◽  
Membrane Lipid ◽  
Human Erythrocytes ◽  
Binding Ability ◽  
Cholesterol Binding

Vibrio cholerae cytolysin (VCC) is a β-barrel pore-forming toxin with potent membrane-damaging cell-killing activity. Previous studies employing the model membranes of lipid vesicles (liposomes) have shown that pore formation by VCC requires the presence of cholesterol in the liposome membranes. However, the exact role of cholesterol in the mode of action of VCC still remains unclear. Most importantly, implication of cholesterol, if any, in regulating the pore-formation mechanism of VCC in the biomembranes of eukaryotic cells remains unexplored. Here, we show that the presence of cholesterol promotes the interaction of VCC with the membrane lipid bilayer, when non-lipid-dependent interactions are absent. However, in the case of biomembranes of human erythrocytes, where accessory interactions are available, cholesterol appears to play a less critical role in the binding step. Nevertheless, in the absence of an optimal level of membrane cholesterol in the human erythrocytes, membrane-bound fraction of the toxin remains trapped in the form of abortive oligomeric assembly, devoid of functional pore-forming activity. Our study also shows that VCC exhibits a prominent propensity to associate with the cholesterol-rich membrane micro-domains of human erythrocytes. Interestingly, mutation of the cholesterol-binding ability of VCC does not block association with the cholesterol-rich membrane micro-domains on human erythrocytes. Based on these results, we propose that the specific cholesterol-binding ability of VCC does not appear to dictate its association with the cholesterol-rich micro-domains on human erythrocytes. Rather, targeting of VCC toward the membrane micro-domains of human erythrocytes possibly acts to facilitate the cholesterol-dependent pore-formation mechanism of the toxin.

Mechanistic Insights into Pore Formation by an α-Pore Forming Toxin: Protein and Lipid Bilayer Interactions of Cytolysin A

2020 ◽  
Vol 54 (1) ◽  
pp. 120-131
Author(s):  
Pradeep Sathyanarayana ◽  
Sandhya S. Visweswariah ◽  
K. Ganapathy Ayappa
Keyword(s):  
Lipid Bilayer ◽  
Pore Formation ◽  
Toxin Protein

scholarly journals PHLIP ARG-Mutant Interactions with the Membrane Lipid Bilayer

2021 ◽  
Vol 120 (3) ◽  
pp. 232a
Author(s):  
Hannah M. Visca ◽  
Oleg A. Andreev ◽  
Yana K. Reshetnyak
Keyword(s):  
Lipid Bilayer ◽  
Membrane Lipid ◽  
Membrane Lipid Bilayer

scholarly journals Dual modes of membrane binding direct pore formation by Streptolysin O

2015 ◽  
Vol 97 (6) ◽  
pp. 1036-1050 ◽  
Author(s):  
Cara C. Mozola ◽  
Michael G. Caparon
Keyword(s):  
Pore Formation ◽  
Membrane Binding ◽  
Streptolysin O

From B to A: making an essential cofactor in a human parasite

2017 ◽  
Vol 474 (18) ◽  
pp. 3089-3092
Author(s):  
Naomi S. Morrissette ◽  
Celia W. Goulding
Keyword(s):  
Cytochrome C ◽  
Trypanosoma Cruzi ◽  
Cytochrome C Oxidase ◽  
Human Disease ◽  
Recent Issue ◽  
Enzyme Reactions ◽  
Human Parasite ◽  
Biochemical Journal ◽  
Eukaryotic Organisms ◽  
Subsequent Activity

Trypanosomatids are parasitic eukaryotic organisms that cause human disease. These organisms have complex lifestyles; cycling between vertebrate and insect hosts and alternating between two morphologies; a replicating form and an infective, nonreplicating one. Because trypanosomatids are one of the few organisms that do not synthesize the essential cofactor, heme, these parasites sequester the most common form, heme B, from their hosts. Once acquired, the parasites derivatize heme B to heme A by two sequential enzyme reactions. Although heme C is found in many cytochrome c and c1 proteins, heme A is the cofactor of only one known protein, cytochrome c oxidase (CcO). In a recent issue of the Biochemical Journal, Merli et al. [Biochem. J. (2017) 474, 2315–2332] demonstrate that the final step in the synthesis of heme A by heme A synthase (TcCox15) and the subsequent activity of CcO are essential for infectivity and replication of Trypanosoma cruzi.

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.

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