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Necrotic cell death in C. elegans requires the function of calreticulin and regulators of Ca(2+) release from the endoplasmic reticulum.

Neuron | Sep 27, 2001

http://www.ncbi.nlm.nih.gov/pubmed/11580896

In C. elegans, a hyperactivated MEC-4(d) ion channel induces necrotic-like neuronal death that is distinct from apoptosis. We report that null mutations in calreticulin suppress both mec-4(d)-induced cell death and the necrotic cell death induced by expression of a constitutively activated Galpha(S) subunit. RNAi-mediated knockdown of calnexin, mutations in the ER Ca(2+) release channels unc-68 (ryanodine receptor) or itr-1 (inositol 1,4,5 triphosphate receptor), and pharmacological manipulations that block ER Ca(2+) release also suppress death. Conversely, thapsigargin-induced ER Ca(2+) release can restore mec-4(d)-induced cell death when calreticulin is absent. We conclude that high [Ca(2+)](i) is a requirement for necrosis in C. elegans and suggest that an essential step in the death mechanism is release of ER-based Ca(2+) stores. ER-driven Ca(2+) release has previously been implicated in mammalian necrosis, suggesting necrotic death mechanisms may be conserved.

Pubmed ID: 11580896 RIS Download

Mesh terms: Amino Acid Sequence | Animals | Animals, Genetically Modified | Caenorhabditis elegans | Caenorhabditis elegans Proteins | Calcium Channels | Calcium Signaling | Calcium-Binding Proteins | Calnexin | Calreticulin | Cell Size | Chromosome Mapping | Endoplasmic Reticulum | Helminth Proteins | Heterotrimeric GTP-Binding Proteins | Homeostasis | Humans | Inositol 1,4,5-Trisphosphate Receptors | Ion Transport | Larva | Membrane Proteins | Molecular Sequence Data | Mutation | Necrosis | Nerve Degeneration | Nerve Tissue Proteins | Neurons | Receptors, Cytoplasmic and Nuclear | Recombinant Fusion Proteins | Ribonucleoproteins | Ryanodine Receptor Calcium Release Channel | Sequence Alignment | Sequence Homology, Amino Acid | Structure-Activity Relationship | Thapsigargin | Touch