Lysenin, a unique sphingomyelin‐binding protein

Shakor, Abo Bakr Abdel; Czuryło, Edward A.; Sobota, Andrzej

doi:10.1016/s0014-5793(03)00330-2

Cited by 52 publications

(37 citation statements)

References 59 publications

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“…Lysenin comprises a family of proteins together with lysenin-related proteins 1 and 2 (14,16,55). Recently we have shown that lysenin recognizes SM in a distribution-dependent manner (15).…”

Section: Discussionmentioning

confidence: 99%

Spatial and Functional Heterogeneity of Sphingolipid-rich Membrane Domains

Kiyokawa

Baba

Otsuka

et al. 2005

Journal of Biological Chemistry

161

168

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Little is known about the organization of lipids in biomembranes. Lipid rafts are defined as sphingolipidand cholesterol-rich clusters in the membrane. Details of the lipid distribution of lipid rafts are not well characterized mainly because of a lack of appropriate probes. Ganglioside GM1-specific protein, cholera toxin, has long been the only lipid probe of lipid rafts. Recently it was shown that earthworm toxin, lysenin, specifically recognizes sphingomyelin-rich membrane domains. Binding of lysenin to sphingomyelin is accompanied by the oligomerization of the toxin that leads to pore formation in the target membrane. In this study, we generated a truncated lysenin mutant that does not oligomerize and thus is non-toxic. Using this mutant lysenin, we showed that plasma membrane sphingomyelin-rich domains are spatially distinct from ganglioside GM1-rich membrane domains in Jurkat T cells. Like T cell receptor activation and crosslinking of GM1, cross-linking of sphingomyelin induced calcium influx and ERK phosphorylation in the cell. However, unlike CD3 or GM1, cross-linking of sphingomyelin did not induce significant protein tyrosine phosphorylation. Combination of lysenin and sphingomyelinase treatment suggested the involvement of G-protein-coupled receptor in sphingomyelinmediated signal transduction. These results thus suggest that the sphingomyelin-rich domain provides a functional signal cascade platform that is distinct from those provided by T cell receptor or GM1. Our study therefore elucidates the spatial and functional heterogeneity of lipid rafts.

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Section: Discussionmentioning

confidence: 99%

Spatial and Functional Heterogeneity of Sphingolipid-rich Membrane Domains

Kiyokawa

Baba

Otsuka

et al. 2005

Journal of Biological Chemistry

161

168

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“…Sphingomyelin levels were also assessed by the binding of lysenin, a protein with high specificity for sphingomyelin, to cell membranes (28,29). KMA-positive (ARH-77_100 and JJN-3 cells) and -negative cell lines (ARH-77_neg and NCI-H929 cells) were incubated with biotinylated lysenin followed by staining with streptavidin-allophycocyanin.…”

Section: Kma Expression Is Sphingomyelin Dependentmentioning

confidence: 99%

Free Ig Light Chains Interact with Sphingomyelin and Are Found on the Surface of Myeloma Plasma Cells in an Aggregated Form

Hutchinson

Ramsland

Jones

et al. 2010

The Journal of Immunology

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“…To answer this question, we focused our attention on lysenin, a 297 amino acid PFT extracted from Eisenia foetida, which inserts hexameric pores (∼3 nm diameter) in artificial and natural lipid membranes containing sphingomyelin (SM) [41][42][43][44][45]. Several remarkable features make lysenin an excellent candidate for such studies.…”

Section: Introductionmentioning

confidence: 99%

Purinergic control of lysenin’s transport and voltage-gating properties

Bryant

Shrestha

Carnig

et al. 2016

Purinergic Signalling

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Lysenin, a pore-forming protein extracted from the coelomic fluid of the earthworm Eisenia foetida, manifests cytolytic activity by inserting large conductance pores in host membranes containing sphingomyelin. In the present study, we found that adenosine phosphates control the biological activity of lysenin channels inserted into planar lipid membranes with respect to their macroscopic conductance and voltage-induced gating. Addition of ATP, ADP, or AMP decreased the macroscopic conductance of lysenin channels in a concentration-dependent manner, with ATP being the most potent inhibitor and AMP the least. ATP removal from the bulk solutions by buffer exchange quickly reinstated the macroscopic conductance and demonstrated reversibility. Singlechannel experiments pointed to an inhibition mechanism that most probably relies on electrostatic binding and partial occlusion of the channel-conducting pathway, rather than ligand gating induced by the highly charged phosphates. The Hill analysis of the changes in macroscopic conduction as a function of the inhibitor concentration suggested cooperative binding as descriptive of the inhibition process. Ionic screening significantly reduced the ATP inhibitory efficacy, in support of the electrostatic binding hypothesis. In addition to conductance modulation, purinergic control over the biological activity of lysenin channels has also been observed to manifest as changes of the voltage-induced gating profile. Our analysis strongly suggests that not only the inhibitor's charge but also its ability to adopt a folded conformation may explain the differences in the observed influence of ATP, ADP, and AMP on lysenin's biological activity.

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Lysenin, a unique sphingomyelin‐binding protein

Cited by 52 publications

References 59 publications

Spatial and Functional Heterogeneity of Sphingolipid-rich Membrane Domains

Spatial and Functional Heterogeneity of Sphingolipid-rich Membrane Domains

Free Ig Light Chains Interact with Sphingomyelin and Are Found on the Surface of Myeloma Plasma Cells in an Aggregated Form

Purinergic control of lysenin’s transport and voltage-gating properties

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