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.

scholarly journals Emerging roles of PLCγ1 in endothelial biology

2021 ◽  
Vol 14 (694) ◽  
pp. eabc6612
Author(s):  
Dongying Chen ◽  
Michael Simons
Keyword(s):  
Tyrosine Kinases ◽  
Second Messengers ◽  
Critical Role ◽  
Physiological Role ◽  
Membrane Lipid ◽  
Molecular Function ◽  
Signal Transducer ◽  
Deficient Animal ◽  
Unique Protein

Phospholipase C γ1 (PLCγ1) is a member of the PLC family that functions as signal transducer by hydrolyzing membrane lipid to generate second messengers. The unique protein structure of PLCγ1 confers a critical role as a direct effector of VEGFR2 and signaling mediated by other receptor tyrosine kinases. The distinct vascular phenotypes in PLCγ1-deficient animal models and the gain-of-function mutations of PLCγ1 found in human endothelial cancers point to a major physiological role of PLCγ1 in the endothelial system. In this review, we discuss aspects of physiological and molecular function centering around PLCγ1 in the context of endothelial cells and provide a perspective for future investigation.

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.

scholarly journals Role of membrane lipids in cold agglutination of human erythrocytes

Blood ◽  
1982 ◽  
Vol 60 (2) ◽  
pp. 340-345
Author(s):  
M Flamm ◽  
MK Basu ◽  
D Schachter ◽  
JF Bertles ◽  
A Maniatis
Keyword(s):  
Membrane Lipids ◽  
Relative Equilibrium ◽  
Membrane Lipid ◽  
Probit Analysis ◽  
Human Erythrocytes ◽  
Cholesterol Depletion ◽  
Lipid Domain ◽  
Lipid Fluidity ◽  
Normal Human

The membrane lipid fluidity of normal human erythrocytes was modified by enrichment and depletion in cholesterol, and the expression of I and SP1 antigens was assayed by quantitative hemagglutination from 4 degrees to 24 degrees C by use of a continuous flow system. Below 16 degrees--18 degrees C, cholesterol enrichment increased and cholesterol depletion decreased percent agglutination. As temperatures approached approximately 18 degrees--20 degrees C, differences in agglutination between modified and unmodified erythrocytes became insignificant despite marked differences in lipid fluidity at that temperature. Thus, fluidity changes alone cannot be responsible for the effect of membrane cholesterol on cold agglutination. In an additional study, the temperature dependence of a relative equilibrium association constant, estimated by probit analysis of percent agglutination at various antisera concentrations, was biphasic with a sharp break at 16 degrees C. Our studies are consistent with the hypothesis that I and Sp1 antigens preferentially partition into a lipid domain that forms during lateral phase separation of membrane lipid developing at low temperature. A resulting increase in antigen density would then become responsible for augmented agglutination by specific antibody.

Highly Reversible Sodiation of Tin in Glyme Electrolytes: The Critical Role of the Solid Electrolyte Interphase and Its Formation Mechanism

2019 ◽  
Vol 12 (3) ◽  
pp. 3697-3708 ◽  
Author(s):  
Bingsheng Qin ◽  
Alexander Schiele ◽  
Zenonas Jusys ◽  
Alessandro Mariani ◽  
Thomas Diemant ◽  
...  
Keyword(s):  
Solid Electrolyte ◽  
Formation Mechanism ◽  
Critical Role ◽  
Solid Electrolyte Interphase

scholarly journals Role of membrane lipids in cold agglutination of human erythrocytes

Blood ◽  
1982 ◽  
Vol 60 (2) ◽  
pp. 340-345 ◽  
Author(s):  
M Flamm ◽  
MK Basu ◽  
D Schachter ◽  
JF Bertles ◽  
A Maniatis
Keyword(s):  
Membrane Lipids ◽  
Relative Equilibrium ◽  
Membrane Lipid ◽  
Probit Analysis ◽  
Human Erythrocytes ◽  
Cholesterol Depletion ◽  
Lipid Domain ◽  
Lipid Fluidity ◽  
Normal Human

Abstract The membrane lipid fluidity of normal human erythrocytes was modified by enrichment and depletion in cholesterol, and the expression of I and SP1 antigens was assayed by quantitative hemagglutination from 4 degrees to 24 degrees C by use of a continuous flow system. Below 16 degrees--18 degrees C, cholesterol enrichment increased and cholesterol depletion decreased percent agglutination. As temperatures approached approximately 18 degrees--20 degrees C, differences in agglutination between modified and unmodified erythrocytes became insignificant despite marked differences in lipid fluidity at that temperature. Thus, fluidity changes alone cannot be responsible for the effect of membrane cholesterol on cold agglutination. In an additional study, the temperature dependence of a relative equilibrium association constant, estimated by probit analysis of percent agglutination at various antisera concentrations, was biphasic with a sharp break at 16 degrees C. Our studies are consistent with the hypothesis that I and Sp1 antigens preferentially partition into a lipid domain that forms during lateral phase separation of membrane lipid developing at low temperature. A resulting increase in antigen density would then become responsible for augmented agglutination by specific antibody.

scholarly journals Critical Role of Lipid Scramblase TMEM16F in Phosphatidylserine Exposure and Repair of Plasma Membrane after Pore Formation

Cell Reports ◽  
2020 ◽  
Vol 30 (4) ◽  
pp. 1129-1140.e5 ◽  
Author(s):  
Ning Wu ◽  
Vitalij Cernysiov ◽  
Dominique Davidson ◽  
Hua Song ◽  
Jianlong Tang ◽  
...  
Keyword(s):  
Plasma Membrane ◽  
Pore Formation ◽  
Critical Role ◽  
Phosphatidylserine Exposure

The Membrane Lipid Cholesterol Modulates Anesthetic Actions on a Human Brain Ion Channel 

1995 ◽  
Vol 82 (3) ◽  
pp. 749-758 ◽  
Author(s):  
Benno Rehberg ◽  
Bernd W. Urban ◽  
Daniel S. Duch
Keyword(s):  
Human Brain ◽  
Sodium Channels ◽  
Lipid Composition ◽  
Membrane Lipids ◽  
Critical Role ◽  
Cholesterol Content ◽  
Membrane Lipid ◽  
Model Systems ◽  
The Impact

Background Molecular theories of general anesthesia often are divided into two categories: (1) Anesthetics may bind specifically to proteins, such as ionic channels, and alter their function directly, and (2) anesthetics may alter the functions of integral membrane proteins indirectly through modification of the physical properties of the membrane. Recent studies have provided evidence that anesthetics can bind to proteins and modify their function directly, bringing into question the role of the membrane in anesthetic interactions. To reexamine the role of membrane lipids in anesthetic interactions, an experimental approach was used in which the membrane lipid composition could be systematically altered and the impact on anesthetic interactions with potential targets examined. Methods Sodium channels from human brain cortex were incorporated into planar lipid bilayers with increasing cholesterol content. The anesthetic suppression of these channels by pentobarbital was quantitatively examined by single channel measurements under voltage-clamp conditions. Results Changes in cholesterol content had no effect on measured channel properties in the absence of anesthetic. In the presence of pentobarbital, however, cholesterol inhibited anesthetic suppression of channel ionic currents, with 1.9% (weight/weight, corresponding to 3.5 mol%) cholesterol decreasing anesthetic suppression of sodium channels by half. Conclusions These results support a critical role for the lipid membrane in some anesthetic actions and further indicate that differences in lipid composition must be considered in the interpretation of results when comparing the anesthetic potencies of potential targets in model systems.

The Role of the SLP in Autism Spectrum Disorder Screening and Assessment

2008 ◽  
Vol 15 (2) ◽  
pp. 50-59 ◽  
Author(s):  
Amy Philofsky
Keyword(s):  
Language Development ◽  
Critical Role ◽  
Children With Autism ◽  
Autism Spectrum ◽  
Children With Asd ◽  
Prevalence Estimates ◽  
Notable Increase ◽  
Screening Assessment ◽  
Critical Components

AbstractRecent prevalence estimates for autism have been alarming as a function of the notable increase. Speech-language pathologists play a critical role in screening, assessment and intervention for children with autism. This article reviews signs that may be indicative of autism at different stages of language development, and discusses the importance of several psychometric properties—sensitivity and specificity—in utilizing screening measures for children with autism. Critical components of assessment for children with autism are reviewed. This article concludes with examples of intervention targets for children with ASD at various levels of language development.

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