Lysenin: a sphingomyelin specific pore-forming toxin.

Biochim Biophys Acta

Supra-Biomolecular System Research Group, RIKEN (Institute of Physical and Chemical Research) Frontier Research System, 2-1, Hirosawa, Wako-shi, Saitama 351-0198, Japan.

Published: March 2008

Sphingomyelin is a major sphingolipid in mammalian cells. Recent results indicate that sphingomyelin is a reservoir of lipid second messengers, ceramide and sphingosine-1-phosphate. Sphingomyelin is also a major component of sphingolipid and cholesterol-rich membrane domains (lipid rafts). Lysenin is a pore-forming toxin that specifically binds sphingomyelin. The binding of lysenin to sphingomyelin is dependent on the membrane distribution of the lipid, i.e. the toxin selectively binds sphingomyelin clusters. Development of a non-toxic lysenin mutant revealed the spatial and functional heterogeneity of sphingolipid-rich membrane domains.

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http://dx.doi.org/10.1016/j.bbagen.2007.09.001DOI Listing

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Article Synopsis
  • Very few proteins specifically bind to certain lipids, but lipid-targeting pore forming toxins (PFTs) are effective tools for studying lipid distribution in cell membranes.
  • This chapter focuses on the sphingomyelin-binding PFT lysenin (Lys), its non-toxic mutant (NT-Lys), and a new protein called nakanori that binds to sphingomyelin and cholesterol.
  • The authors detail the preparation of NT-Lys for use in advanced imaging techniques, like optical and super-resolution microscopy, and the observation of tiny lipid domains using electron microscopy with nakanori and another protein, MBP-Lys.
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Lipid rafts are dynamic assemblies of glycosphingolipids, sphingomyelin, cholesterol, and specific proteins which are stabilized into platforms involved in the regulation of vital cellular processes. The rafts at the cell surface play important functions in signal transduction. Recent reports have demonstrated that lipid rafts are spatially and compositionally heterogeneous in the single-cell membrane.

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