scholarly journals Functions of cholera toxin B-subunit as a raft cross-linker

2015 ◽  
Vol 57 ◽  
pp. 135-145 ◽  
Author(s):  
Charles A. Day ◽  
Anne K. Kenworthy
Keyword(s):  
Cholera Toxin ◽  
Lipid Rafts ◽  
Current Evidence ◽  
Cross Linking ◽  
Cholera Toxin B Subunit ◽  
Toxin B ◽  
Cholera Toxin B ◽  
B Subunit ◽  
Functional Consequences ◽  
Cross Links

Lipid rafts are putative complexes of lipids and proteins in cellular membranes that are proposed to function in trafficking and signalling events. CTxB (cholera toxin B-subunit) has emerged as one of the most studied examples of a raft-associated protein. Consisting of the membrane-binding domain of cholera toxin, CTxB binds up to five copies of its lipid receptor on the plasma membrane of the host cell. This multivalency of binding gives the toxin the ability to reorganize underlying membrane structure by cross-linking otherwise small and transient lipid rafts. CTxB thus serves as a useful model for understanding the properties and functions of protein-stabilized domains. In the present chapter, we summarize current evidence that CTxB associates with and cross-links lipid rafts, discuss how CTxB binding modulates the architecture and dynamics of membrane domains, and describe the functional consequences of this cross-linking behaviour on toxin uptake into cells via endocytosis.

scholarly journals Cholera Toxin B-Subunit Prevents Activation and Proliferation of Human CD4+ T Cells by Activation of a Neutral Sphingomyelinase in Lipid Rafts

2005 ◽  
Vol 175 (9) ◽  
pp. 5637-5648 ◽  
Author(s):  
Alexandre K. Rouquette-Jazdanian ◽  
Arnaud Foussat ◽  
Laurence Lamy ◽  
Claudette Pelassy ◽  
Patricia Lagadec ◽  
...  
Keyword(s):  
T Cells ◽  
Cholera Toxin ◽  
Lipid Rafts ◽  
Cd4 T Cells ◽  
Cholera Toxin B Subunit ◽  
Toxin B ◽  
Cholera Toxin B ◽  
Neutral Sphingomyelinase ◽  
B Subunit

scholarly journals High-Resolution FRET Microscopy of Cholera Toxin B-Subunit and GPI-anchored Proteins in Cell Plasma Membranes

2000 ◽  
Vol 11 (5) ◽  
pp. 1645-1655 ◽  
Author(s):  
Anne K. Kenworthy ◽  
Nadezda Petranova ◽  
Michael Edidin
Keyword(s):  
Plasma Membrane ◽  
Cell Surface ◽  
Cholera Toxin ◽  
Lipid Rafts ◽  
Plasma Membranes ◽  
Membrane Lipid ◽  
Cholera Toxin B Subunit ◽  
Toxin B ◽  
Cholera Toxin B ◽  
B Subunit

“Lipid rafts” enriched in glycosphingolipids (GSL), GPI-anchored proteins, and cholesterol have been proposed as functional microdomains in cell membranes. However, evidence supporting their existence has been indirect and controversial. In the past year, two studies used fluorescence resonance energy transfer (FRET) microscopy to probe for the presence of lipid rafts; rafts here would be defined as membrane domains containing clustered GPI-anchored proteins at the cell surface. The results of these studies, each based on a single protein, gave conflicting views of rafts. To address the source of this discrepancy, we have now used FRET to study three different GPI-anchored proteins and a GSL endogenous to several different cell types. FRET was detected between molecules of the GSL GM1 labeled with cholera toxin B-subunit and between antibody-labeled GPI-anchored proteins, showing these raft markers are in submicrometer proximity in the plasma membrane. However, in most cases FRET correlated with the surface density of the lipid raft marker, a result inconsistent with significant clustering in microdomains. We conclude that in the plasma membrane, lipid rafts either exist only as transiently stabilized structures or, if stable, comprise at most a minor fraction of the cell surface.

scholarly journals Spray-Dried Formulation of Epicertin, a Recombinant Cholera Toxin B Subunit Variant That Induces Mucosal Healing

Pharmaceutics ◽  
2021 ◽  
Vol 13 (4) ◽  
pp. 576
Author(s):  
Micaela A. Reeves ◽  
Joshua M. Royal ◽  
David A. Morris ◽  
Jessica M. Jurkiewicz ◽  
Nobuyuki Matoba ◽  
...  
Keyword(s):  
Gastric Acid ◽  
Cholera Toxin ◽  
Oral Formulation ◽  
Size Exclusion ◽  
Cholera Toxin B Subunit ◽  
Toxin B ◽  
Cholera Toxin B ◽  
B Subunit ◽  
Enteric Coated ◽  
Spray Dried

Epicertin (EPT) is a recombinant variant of the cholera toxin B subunit, modified with a C-terminal KDEL endoplasmic reticulum retention motif. EPT has therapeutic potential for ulcerative colitis treatment. Previously, orally administered EPT demonstrated colon epithelial repair activity in dextran sodium sulfate (DSS)-induced acute and chronic colitis in mice. However, the oral dosing requires cumbersome pretreatment with sodium bicarbonate to conserve the acid-labile drug substance while transit through the stomach, hampering its facile application in chronic disease treatment. Here, we developed a solid oral formulation of EPT that circumvents degradation in gastric acid. EPT was spray-dried and packed into enteric-coated capsules to allow for pH-dependent release in the colon. A GM1-capture KDEL-detection ELISA and size-exclusion HPLC indicated that EPT powder maintains activity and structural stability for up to 9 months. Capsule disintegration tests showed that EPT remained encapsulated at pH 1 but was released over 180 min at pH 6.8, the approximate pH of the proximal colon. An acute DSS colitis study confirmed the therapeutic efficacy of encapsulated EPT in C57BL/6 mice upon oral administration without gastric acid neutralization pretreatment compared to vehicle-treated mice (p < 0.05). These results provide a foundation for an enteric-coated oral formulation of spray-dried EPT.

Synthesis of Lactose Dendrimers and Multivalency Effects in Binding to the Cholera Toxin B Subunit

2001 ◽  
Vol 2001 (24) ◽  
pp. 4685 ◽  
Author(s):  
Ioannis Vrasidas ◽  
Nico J. de Mol ◽  
Rob M. J. Liskamp ◽  
Roland J. Pieters
Keyword(s):  
Cholera Toxin ◽  
Cholera Toxin B Subunit ◽  
Toxin B ◽  
Cholera Toxin B ◽  
B Subunit
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