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Sci. STKE, 9 October 2001
Vol. 2001, Issue 103, p. tw367
[DOI: 10.1126/stke.2001.103.tw367]

EDITORS' CHOICE

Necrosis ER Calcium Critical for Necrosis

Necrosis is cell death that results from injury or cell stress and is biochemically and morphologically distinct from apoptosis, or programmed cell death. In the worm Caenorhabditis elegans, activated mutants of degenerin channels, such as the Na+ channel, can cause necrotic cell death in the cells expressing the mutant channels. Xu et al. identified calreticulin in a screen for mutations that suppress necrosis in a degenerin Na+ channel mutant background. Calreticulin mutants suppressed necrosis in neurons and muscles and in response to two different necrosis-inducing stresses: activated Na+ channels and ectopic expression of activated Gαs. Calreticulin mutants could not suppress necrosis induced by activated Ca2+ channels, suggesting that calreticulin was affecting calcium homeostasis not protein synthesis. Loss of function mutants of the inositol triphosphate receptor or the ryanodine receptor [two calcium release channels in the endoplasmic reticulum (ER)] or suppression of expression of calnexin were all also able to suppress necrosis in the activated Na+ channel mutants. Pharmacological manipulations that decreased ER calcium levels or ER calcium release also inhibited necrosis. Thus, ER calcium release and buffering capacity controlled by the calcium binding proteins calreticulin and calnexin appear essential for stimulating necrosis by stresses not involving calcium influx across the plasma membrane.

K. Xu, N. Tavernarakis, M. Driscoll, Necrotic cell death in C. elegans requires the function of calreticulin and regulators of Ca2+ release from the endoplasmic reticulum. Neuron 31, 957-971 (2001). [Online Journal]

Citation: ER Calcium Critical for Necrosis. Sci. STKE 2001, tw367 (2001).


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