Plasma membrane reorganization: A glycolipid gateway for microbes

Abstract

Ligand-receptor interactions, which represent the core for cell signaling and internalization processes are largely affected by the spatial configuration of host cell receptors. There is a growing piece of evidence that receptors are not homogeneously distributed within the plasma membrane, but are rather pre-clustered in nanodomains, or clusters are formed upon ligand binding. Pathogens have evolved many strategies to evade the host immune system and to ensure their survival by hijacking plasma membrane receptors that are most often associated with lipid rafts. In this review, we discuss the early stage molecular and physiological events that occur following ligand binding to host cell glycolipids. The ability of various biological ligands (e.g. toxins, lectins, viruses or bacteria) that bind to glycolipids to induce their own uptake into mammalian cells by creating negative membrane curvature and membrane invaginations is explored. We highlight recent trends in understanding nanoscale plasma membrane (re-)organization and present the benefits of using synthetic membrane systems. This article is part of a Special Issue entitled: Nanoscale membrane organisation and signalling.

Heat stress: A risk factor for skin carcinogenesis

“…CPDs and 6-4PPs are formed as a result of a photochemical reaction between UVB and the DNA, leading to covalent linkage of adjacent thymine dimers (Figure 1.2), inducing significant changes in the nucleotide structure (Besarutinia et al, 2004;Yogianti et al, 2012). CPD formation generally occurs at sites of methylated cytosines, and thus an abundance of methylated cytosines in a particular DNA region increases susceptibility to UV radiation-induced damage at these sites (Aigal et al, 2015;Brenner et al, 2009). Thus, CpG islands, DNA regions containing 5-methylcytosines, are hotspots for such DNA mutations (Ikehata et al, 2003;Ikehata and Ono, 2011).…”

Shiga toxin glycosphingolipid receptors of Vero-B4 kidney epithelial cells and their membrane microdomain lipid environment

“…GSLs preferentially distribute to phase-separated microdomains in the outer leafl et of the plasma membrane, which are suggested to operate as attachment platforms for host pathogens and their toxins on epithelial cells ( 57,92,93 ) to gain entry into cells and retrograde routing to intracellular targets in the cytosol ( 35,56,94 ). The analysis of Average values of triplicate TLC densitometric determinations of three separate experiments of each analyzed GSL in respective sucrose density gradient fractions are listed (see Fig.…”

“…toxin or Stxs from pathogenic E. coli ( 35,56,57 ). Cholesterol-rich lipid rafts make them relatively resistant to solubilization by nonionic detergents, allowing for the isolation of detergent-resistant membranes (DRMs) from low buoyant density fractions after sucrose density ultracentrifugation ( 58 ).…”

Membrane assembly of Shiga toxin glycosphingolipid receptors and toxin refractiveness of MDCK II epithelial cells

“…Plasma membrane segregation into microdomains is well recognized as a functional requirement for binding of pathogens and toxins to gain entry into cells (27)(28)(29)(30)(31). Shiga toxins (Stxs) from pathogenic Stx-producing Escherichia coli (STEC) bind to lipid raft-associated GSL receptors on the surface of target cells, followed by endocytosis and retrograde transport to intracellular targets (32)(33)(34).…”