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

Abstract

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.

Cholesterol-induced suppression of membrane elastic fluctuations at the atomistic level

“…Cholesterol is one such component that may not be uniformly distributed in cellular membranes, whose distribution entails liquid-ordered raft-like domains (Ackerman and Feigenson, 2015; Amazon and Feigenson, 2014; Epand, 1998; Epand, 2006; Feigenson, 2015; Goñi et al, 2008; Konyakhina and Feigenson, 2016; Scheidt et al, 2013; Sodt et al, 2014). Such raft-like domains have garnered considerable attention as platforms for signaling proteins in cellular biology and pharmacology (Brown and London, 1998; Day and Kenworthy, 2015; Golebiewska and Scarlata, 2010; Klose et al, 2013; Simons and Gerl, 2010; Simons and Sampaio, 2011; Song et al, 2014; Surma et al, 2012). The concept that biomembranes are two-dimensional fluids with randomly distributed proteins (the fluid mosaic model) is challenged by the hypothesis that cellular membranes may contain such areas of lateral segregation (Bartels et al, 2008; Camley and Brown, 2010; Edidin, 2003; Feigenson, 2015; Keller and McConnell, 1999; Korade and Kenworthy, 2008; Leftin et al, 2013; Leftin et al, 2014a; Lingwood and Simons, 2010; Meinhardt et al, 2013; Polozov and Gawrisch, 2006; Quinn, 2013; Simons and Gerl, 2010; Veatch et al, 2007; Wassall and Stillwell, 2009).…”

β‐elemene increases the sensitivity of gastric cancer cells to TRAIL by promoting the formation of DISC in lipid rafts

“…Recently it has been widely used as a marker of membrane lipid rafts, which are membrane microdomains enriched with cholestrol and sphingolipids. CTxB binds up to five copies of its lipid receptor on the plasma membrane of the host cell, so CTxB associates with and cross‐links lipid rafts (Day and Kenworthy, ). In the present study, CTxB was used to detected the lipid rafts.…”

Glycolipid Crosslinking is Required for Cholera Toxin to Partition into and Stabilize Ordered Domains

“…Its homopentameric B subunit (CTxB) recognizes and binds up to five molecules of its glycolipid receptor ganglioside GM1 (5). Previous studies have established that CTxB partitions into the l o phase, defining it as a raft marker (6)(7)(8).…”

“…Cholera toxin (CTx), an AB5 toxin, is a well-known lipid raft marker that has been used extensively to study the origins and functionality of lipid rafts (5). Its homopentameric B subunit (CTxB) recognizes and binds up to five molecules of its glycolipid receptor ganglioside GM1 (5).…”