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Novel toxin receptor discovered for ulcer-causing stomach pathogen
Date:5/23/2008

rily of lipids and proteins and are designed to keep things out. Some molecules can penetrate them, but most can do so only after binding to a specific membrane component, called a receptor. Receptors sometimes act as keys that open channels through a membrane, or they function as signaling molecules, communicating to other components in the cell.

Blankes team knew that VacA was latching on to something on the cell surface that was helping it across the membrane.

Other studies had shown that VacA bound to lipids within artificially created membranes, so graduate students Vijay Gupta and Hetal Patel screened a number of lipids for VacA binding and soon found one to which the toxin readily attached. This lipid, called sphingomyelin, is an important and abundant component of the membrane of some animal cells. (Foods such as milk, meat, fish and eggs are dietary sources of sphingomyelin.)

To be considered a receptor, a molecule must meet two criteria, Blanke said. It must bind the agent of interest (in this case VacA) to the cell surface, and it must confer sensitivity to that agent. In other words, a receptor to VacA must be essential to the process by which VacA gets into a cell. If you removed the receptor, or blocked it, the toxin would lose its ability to bind or function. Prior to this study, no molecules on the membrane of human cells had been found that satisfied both criteria as a receptor.

Upon entering cells, VacA spurs the formation of giant vacuoles. These oversized membrane-bound compartments are easy to spot under a microscope and provide a useful indicator of VacA activity in the cell.

To test whether sphingomyelin was a receptor for VacA, Gupta treated cultured human cells with an enzyme that depleted the membranes of sphingomyelin. In the sphingomyelin-depleted cells, the toxin lost its ability to cross into the cells and the giant vacuoles disappeared. When he restored sphingomyelin to the same cell membra
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Contact: Diana Yates
diya@illinois.edu
217-333-5802
University of Illinois at Urbana-Champaign
Source:Eurekalert  

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