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Fixing the hole

Many bacteria attack cells using pore-forming toxins. An efflux of K⁺ through these pores activates lipid synthesis that helps the cells survive, say Laure Gurcel, F. Gisou van der Goot (University of Geneva, Switzerland), and colleagues.

The group's first clue was that treatment of cells with aerolysin, a pore-forming protein from Aeromonas, triggered processing of SREBP-2. Processed SREBP-2 enters the nucleus and induces transcription; its target genes turn on cholesterol and fatty acid biosynthesis.

After testing many candidates for the source of the signal, the researchers added aerolysin in the presence of high K⁺ medium. With K⁺ efflux prevented, the cells did not activate SREBP-2 and died in droves. A K⁺ ionophore, by contrast, was sufficient to induce SREBP-2 activation.

The pathway that emerged leads from K⁺ entry to assembly of two so-called inflammasome complexes. These allow autoproteolysis of caspase-1, leading eventually to the activating proteolysis of SREBP-2, and the induction of SREBP-2 targets such as fatty acid synthase. All these steps were needed to promote cell survival after aerolysin treatment.

The function of the lipid synthesis is uncertain, but a simple plugging of the hole is almost certainly not happening. "The pore we are looking at is extremely stable," says van der Goot. "It's not the surface occupied by the holes that requires synthesis." Instead, repair may involve endocytosis or vesiculation. Either one may require lipid synthesis to drive or replenish the process.

Reference:

Gurcel, L., et al. 2006. Cell. 126:1135–1145.[CrossRef][Medline]

William A. Wells

wellsw{at}rockefeller.edu

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This Article Full Text (PDF, 1106K) Alert me when this article is cited Services Email this article Similar articles in this journal Alert me to new content in the JCB Download to citation manager Citing Articles Citing Articles via CrossRef Citing Articles via Google Scholar Google Scholar Articles by Wells, W. A. Search for Related Content PubMed Articles by Wells, W. A. Social Bookmarking                            What's this?