Forgot Password

If you have forgotten your password you can enter your email here and get a temporary password sent to your email.

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

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


  • Xu K
  • Tavernarakis N
  • Driscoll M



Publication Data

September 27, 2001

Associated Grants

  • Agency: NINDS NIH HHS, Id: NS 34435

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