Pore-forming toxins: Properties, diversity, and uses as tools to image sphingomyelin and ceramide phosphoethanolamine

Abstract

Pore-forming toxins (PFTs) represent a unique class of highly specific lipid-binding proteins. The cytotoxicity of these compounds has been overcome through crystallographic structure and mutation studies, facilitating the development of non-toxic lipid probes. As a consequence, non-toxic PFTs have been utilized as highly specific probes to visualize the diversity and dynamics of lipid nanostructures in living and fixed cells. This review is focused on the application of PFTs and their non-toxic analogs as tools to visualize sphingomyelin and ceramide phosphoethanolamine, two major phosphosphingolipids in mammalian and insect cells, respectively. This article is part of a Special Issue entitled: Pore-Forming Toxins edited by Mauro Dalla Serra and Franco Gambale.

Switching head group selectivity in mammalian sphingolipid biosynthesis by active-site engineering of sphingomyelin synthases

“…NBDC6CPE (NBDCPE) was gener ously provided by Philippe Devaux (Institut de Biologie Physico Chimique, Paris). WEPRO2240 wheat germ extract was from Cell-Free Sciences, Accudenz from Accurate Chemicals and [1,[2][3][4][5][6][7][8][9][10][11][12][13][14] C]ethanolamine hydrochloride (100 Ci/ml, 100-115 mCi/ mmol) from BioTrend. EndoH was from New England Biolabs.…”

Functional studies of aegerolysin and MACPF‐like proteins in Aspergillus niger

“…Recently, ostreolysin A and pleurotolysin A2, along with erylysin A from P. eryngii, were reported to interact even more specifically (K d , 1.2-12 nM) with binary equimolar lipid vesicles composed of CPE and cholesterol, and pleurotolysin A2 was able to bind also CPE-containing vesicles devoid of cholesterol (Bhat et al, 2015). This interaction allowed the use of these aegerolysins as useful molecular markers of the CPE distribution in insect cells and tissues, and for detection of the bloodstream form of Trypanosoma brucei (Bhat et al, 2015;Yamaji-Hasegawa et al, 2016, Panevska et al, 2019. Moreover, when combined with their MACPF protein partner, these Pleurotus aegerolysins can effectively permeabilize lipid vesicles containing physiologically relevant CPE concentrations and insect cells, and can act as potent bioinsecticides against selected coleopteran pests (Panevska et al, 2019).…”

Ostreolysin A/Pleurotolysin B and Equinatoxins: Structure, Function and Pathophysiological Effects of These Pore-Forming Proteins

“…Furthermore, they have been tested as the toxic moiety of immunotoxins targeting at Giardia duodenalis [68]. Their use as molecular probes for sphingomyelin-rich membrane domains seems to be more promising [21,69]. Finally, EqT II has been shown to inhibit endocytosis [41] and to cause membrane reorganization [41,70].…”